Search results for: spherical symmetry
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 547

Search results for: spherical symmetry

37 Development and Characterization of Topical 5-Fluorouracil Solid Lipid Nanoparticles for the Effective Treatment of Non-Melanoma Skin Cancer

Authors: Sudhir Kumar, V. R. Sinha

Abstract:

Background: The topical and systemic toxicity associated with present nonmelanoma skin cancer (NMSC) treatment therapy using 5-Fluorouracil (5-FU) make it necessary to develop a novel delivery system having lesser toxicity and better control over drug release. Solid lipid nanoparticles offer many advantages like: controlled and localized release of entrapped actives, nontoxicity, and better tolerance. Aim:-To investigate safety and efficacy of 5-FU loaded solid lipid nanoparticles as a topical delivery system for the treatment of nonmelanoma skin cancer. Method: Topical solid lipid nanoparticles of 5-FU were prepared using Compritol 888 ATO (Glyceryl behenate) as lipid component and pluronic F68 (Poloxamer 188), Tween 80 (Polysorbate 80), Tyloxapol (4-(1,1,3,3-Tetramethylbutyl) phenol polymer with formaldehyde and oxirane) as surfactants. The SLNs were prepared with emulsification method. Different formulation parameters viz. type and ratio of surfactant, ratio of lipid and ratio of surfactant:lipid were investigated on particle size and drug entrapment efficiency. Results: Characterization of SLNs like–Transmission Electron Microscopy (TEM), Differential Scannig calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Particle size determination, Polydispersity index, Entrapment efficiency, Drug loading, ex vivo skin permeation and skin retention studies, skin irritation and histopathology studies were performed. TEM results showed that shape of SLNs was spherical with size range 200-500nm. Higher encapsulation efficiency was obtained for batches having higher concentration of surfactant and lipid. It was found maximum 64.3% for SLN-6 batch with size of 400.1±9.22 nm and PDI 0.221±0.031. Optimized SLN batches and marketed 5-FU cream were compared for flux across rat skin and skin drug retention. The lesser flux and higher skin retention was obtained for SLN formulation in comparison to topical 5-FU cream, which ensures less systemic toxicity and better control of drug release across skin. Chronic skin irritation studies lacks serious erythema or inflammation and histopathology studies showed no significant change in physiology of epidermal layers of rat skin. So, these studies suggest that the optimized SLN formulation is efficient then marketed cream and safer for long term NMSC treatment regimens. Conclusion: Topical and systemic toxicity associated with long-term use of 5-FU, in the treatment of NMSC, can be minimized with its controlled release with significant drug retention with minimal flux across skin. The study may provide a better alternate for effective NMSC treatment.

Keywords: 5-FU, topical formulation, solid lipid nanoparticles, non melanoma skin cancer

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36 Petrology of the Post-Collisional Dolerites, Basalts from the Javakheti Highland, South Georgia

Authors: Bezhan Tutberidze

Abstract:

The Neogene-Quaternary volcanic rocks of the Javakheti Highland are products of post-collisional continental magmatism and are related to divergent and convergent margins of Eurasian-Afroarabian lithospheric plates. The studied area constitutes an integral part of the volcanic province of Central South Georgia. Three cycles of volcanic activity are identified here: 1. Late Miocene-Early Pliocene, 2. Late Pliocene-Early /Middle/ Pleistocene and 3. Late Pleistocene. An intense basic dolerite magmatic activity occurred within the time span of the Late Pliocene and lasted until at least Late /Middle/ Pleistocene. The age of the volcanogenic and volcanogenic-sedimentary formation was dated by geomorphological, paleomagnetic, paleontological and geochronological methods /1.7-1.9 Ma/. The volcanic area of the Javakheti Highland contains multiple dolerite Plateaus: Akhalkalaki, Gomarethi, Dmanisi, and Tsalka. Petrographic observations of these doleritic rocks reveal fairly constant mineralogical composition: olivine / Fo₈₇.₆₋₈₂.₇ /, plagioclase / Ab₂₂.₈ An₇₅.₉ Or₁.₃; Ab₄₅.₀₋₃₂.₃ An₅₂.₉₋₆₂.₃ Or₂.₁₋₅.₄/. The pyroxene is an augite and may exhibit a visible zoning: / Wo 39.7-43.1 En 43.5-45.2 Fs 16.8-11.7/. Opaque minerals /magnetite, titanomagnetite/ is abundant as inclusions within olivine and pyroxene crystals. The texture of dolerites exhibits intergranular, holocrystalline to ophitic to sub ophitic granular. Dolerites are most common vesicular rocks. Vesicles range in shape from spherical to elongated and in size from 0.5 mm to than 1.5-2 cm and makeup about 20-50 % of the volume. The dolerites have been subjected to considerable alteration. The secondary minerals in the geothermal field are: zeolite, calcite, chlorite, aragonite, clay-like mineral /dominated by smectites/ and iddingsite –like mineral; rare quartz and pumpellyite are present. These vesicles are filled by secondary minerals. In the chemistry, dolerites are the calc-alkalic transition to sub-alkaline with a predominance of Na₂O over K₂O. Chemical analyses indicate that dolerites of all plateaus of the Javakheti Highland have similar geochemical compositions, signifying that they were formed from the same magmatic source by crystallization of olivine basalis magma which less differentiated / ⁸⁷Sr \ ⁸⁶Sr 0.703920-0704195/. There is one argument, which is less convincing, according to which the dolerites/basalts of the Javakheti Highland are considered to be an activity of a mantle plume. Unfortunately, there does not exist reliable evidence to prove this. The petrochemical peculiarities and eruption nature of the dolerites of the Javakheti Plateau point against their plume origin. Nevertheless, it is not excluded that they influence the formation of dolerite producing primary basaltic magma.

Keywords: calc-alkalic, dolerite, Georgia, Javakheti Highland

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35 Deep Learning for SAR Images Restoration

Authors: Hossein Aghababaei, Sergio Vitale, Giampaolo Ferraioli

Abstract:

In the context of Synthetic Aperture Radar (SAR) data, polarization is an important source of information for Earth's surface monitoring. SAR Systems are often considered to transmit only one polarization. This constraint leads to either single or dual polarimetric SAR imaging modalities. Single polarimetric systems operate with a fixed single polarization of both transmitted and received electromagnetic (EM) waves, resulting in a single acquisition channel. Dual polarimetric systems, on the other hand, transmit in one fixed polarization and receive in two orthogonal polarizations, resulting in two acquisition channels. Dual polarimetric systems are obviously more informative than single polarimetric systems and are increasingly being used for a variety of remote sensing applications. In dual polarimetric systems, the choice of polarizations for the transmitter and the receiver is open. The choice of circular transmit polarization and coherent dual linear receive polarizations forms a special dual polarimetric system called hybrid polarimetry, which brings the properties of rotational invariance to geometrical orientations of features in the scene and optimizes the design of the radar in terms of reliability, mass, and power constraints. The complete characterization of target scattering, however, requires fully polarimetric data, which can be acquired with systems that transmit two orthogonal polarizations. This adds further complexity to data acquisition and shortens the coverage area or swath of fully polarimetric images compared to the swath of dual or hybrid polarimetric images. The search for solutions to augment dual polarimetric data to full polarimetric data will therefore take advantage of full characterization and exploitation of the backscattered field over a wider coverage with less system complexity. Several methods for reconstructing fully polarimetric images using hybrid polarimetric data can be found in the literature. Although the improvements achieved by the newly investigated and experimented reconstruction techniques are undeniable, the existing methods are, however, mostly based upon model assumptions (especially the assumption of reflectance symmetry), which may limit their reliability and applicability to vegetation and forest scenarios. To overcome the problems of these techniques, this paper proposes a new framework for reconstructing fully polarimetric information from hybrid polarimetric data. The framework uses Deep Learning solutions to augment hybrid polarimetric data without relying on model assumptions. A convolutional neural network (CNN) with a specific architecture and loss function is defined for this augmentation problem by focusing on different scattering properties of the polarimetric data. In particular, the method controls the CNN training process with respect to several characteristic features of polarimetric images defined by the combination of different terms in the cost or loss function. The proposed method is experimentally validated with real data sets and compared with a well-known and standard approach from the literature. From the experiments, the reconstruction performance of the proposed framework is superior to conventional reconstruction methods. The pseudo fully polarimetric data reconstructed by the proposed method also agree well with the actual fully polarimetric images acquired by radar systems, confirming the reliability and efficiency of the proposed method.

Keywords: SAR image, polarimetric SAR image, convolutional neural network, deep learnig, deep neural network

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34 Tip-Enhanced Raman Spectroscopy with Plasmonic Lens Focused Longitudinal Electric Field Excitation

Authors: Mingqian Zhang

Abstract:

Tip-enhanced Raman spectroscopy (TERS) is a scanning probe technique for individual objects and structured surfaces investigation that provides a wealth of enhanced spectral information with nanoscale spatial resolution and high detection sensitivity. It has become a powerful and promising chemical and physical information detection method in the nanometer scale. The TERS technique uses a sharp metallic tip regulated in the near-field of a sample surface, which is illuminated with a certain incident beam meeting the excitation conditions of the wave-vector matching. The local electric field, and, consequently, the Raman scattering, from the sample in the vicinity of the tip apex are both greatly tip-enhanced owning to the excitation of localized surface plasmons and the lightning-rod effect. Typically, a TERS setup is composed of a scanning probe microscope, excitation and collection optical configurations, and a Raman spectroscope. In the illumination configuration, an objective lens or a parabolic mirror is always used as the most important component, in order to focus the incident beam on the tip apex for excitation. In this research, a novel TERS setup was built up by introducing a plasmonic lens to the excitation optics as a focusing device. A plasmonic lens with symmetry breaking semi-annular slits corrugated on gold film was designed for the purpose of generating concentrated sub-wavelength light spots with strong longitudinal electric field. Compared to conventional far-field optical components, the designed plasmonic lens not only focuses an incident beam to a sub-wavelength light spot, but also realizes a strong z-component that dominants the electric field illumination, which is ideal for the excitation of tip-enhancement. Therefore, using a PL in the illumination configuration of TERS contributes to improve the detection sensitivity by both reducing the far-field background and effectively exciting the localized electric field enhancement. The FDTD method was employed to investigate the optical near-field distribution resulting from the light-nanostructure interaction. And the optical field distribution was characterized using an scattering-type scanning near-field optical microscope to demonstrate the focusing performance of the lens. The experimental result is in agreement with the theoretically calculated one. It verifies the focusing performance of the plasmonic lens. The optical field distribution shows a bright elliptic spot in the lens center and several arc-like side-lobes on both sides. After the focusing performance was experimentally verified, the designed plasmonic lens was used as a focusing component in the excitation configuration of TERS setup to concentrate incident energy and generate a longitudinal optical field. A collimated linearly polarized laser beam, with along x-axis polarization, was incident from the bottom glass side on the plasmonic lens. The incident light focused by the plasmonic lens interacted with the silver-coated tip apex and enhanced the Raman signal of the sample locally. The scattered Raman signal was gathered by a parabolic mirror and detected with a Raman spectroscopy. Then, the plasmonic lens based setup was employed to investigate carbon nanotubes and TERS experiment was performed. Experimental results indicate that the Raman signal is considerably enhanced which proves that the novel TERS configuration is feasible and promising.

Keywords: longitudinal electric field, plasmonics, raman spectroscopy, tip-enhancement

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33 Deep Learning Based Polarimetric SAR Images Restoration

Authors: Hossein Aghababaei, Sergio Vitale, Giampaolo ferraioli

Abstract:

In the context of Synthetic Aperture Radar (SAR) data, polarization is an important source of information for Earth's surface monitoring . SAR Systems are often considered to transmit only one polarization. This constraint leads to either single or dual polarimetric SAR imaging modalities. Single polarimetric systems operate with a fixed single polarization of both transmitted and received electromagnetic (EM) waves, resulting in a single acquisition channel. Dual polarimetric systems, on the other hand, transmit in one fixed polarization and receive in two orthogonal polarizations, resulting in two acquisition channels. Dual polarimetric systems are obviously more informative than single polarimetric systems and are increasingly being used for a variety of remote sensing applications. In dual polarimetric systems, the choice of polarizations for the transmitter and the receiver is open. The choice of circular transmit polarization and coherent dual linear receive polarizations forms a special dual polarimetric system called hybrid polarimetry, which brings the properties of rotational invariance to geometrical orientations of features in the scene and optimizes the design of the radar in terms of reliability, mass, and power constraints. The complete characterization of target scattering, however, requires fully polarimetric data, which can be acquired with systems that transmit two orthogonal polarizations. This adds further complexity to data acquisition and shortens the coverage area or swath of fully polarimetric images compared to the swath of dual or hybrid polarimetric images. The search for solutions to augment dual polarimetric data to full polarimetric data will therefore take advantage of full characterization and exploitation of the backscattered field over a wider coverage with less system complexity. Several methods for reconstructing fully polarimetric images using hybrid polarimetric data can be found in the literature. Although the improvements achieved by the newly investigated and experimented reconstruction techniques are undeniable, the existing methods are, however, mostly based upon model assumptions (especially the assumption of reflectance symmetry), which may limit their reliability and applicability to vegetation and forest scenarios. To overcome the problems of these techniques, this paper proposes a new framework for reconstructing fully polarimetric information from hybrid polarimetric data. The framework uses Deep Learning solutions to augment hybrid polarimetric data without relying on model assumptions. A convolutional neural network (CNN) with a specific architecture and loss function is defined for this augmentation problem by focusing on different scattering properties of the polarimetric data. In particular, the method controls the CNN training process with respect to several characteristic features of polarimetric images defined by the combination of different terms in the cost or loss function. The proposed method is experimentally validated with real data sets and compared with a well-known and standard approach from the literature. From the experiments, the reconstruction performance of the proposed framework is superior to conventional reconstruction methods. The pseudo fully polarimetric data reconstructed by the proposed method also agree well with the actual fully polarimetric images acquired by radar systems, confirming the reliability and efficiency of the proposed method.

Keywords: SAR image, deep learning, convolutional neural network, deep neural network, SAR polarimetry

Procedia PDF Downloads 49
32 Structural Fluxionality of Luminescent Coordination Compounds with Lanthanide Ions

Authors: Juliana A. B. Silva, Caio H. T. L. Albuquerque, Leonardo L. dos Santos, Cristiane K. Oliveira, Ivani Malvestiti, Fernando Hallwass, Ricardo L. Longo

Abstract:

Complexes with lanthanide ions have been extensively studied due to their applications as luminescent, magnetic and catalytic materials as molecular or extended crystals, thin films, glasses, polymeric matrices, ionic liquids, and in solution. NMR chemical shift data in solution have been reported and suggest fluxional structures in a wide range of coordination compounds with rare earth ions. However, the fluxional mechanisms for these compounds are still not established. This structural fluxionality may affect the photophysical, catalytic and magnetic properties in solution. Thus, understanding the structural interconversion mechanisms may aid the design of coordination compounds with, for instance, improved (electro)luminescence, catalytic and magnetic behaviors. The [Eu(btfa)₃bipy] complex, where btfa= 4,4,4-trifluoro-1-phenyl-1,3-butanedionate and bipy= 2,2’-bipiridyl, has a well-defined X-ray crystallographic structure and preliminary 1H NMR data suggested a structural fluxionality. Thus, we have investigated a series of coordination compounds with lanthanide ions [Ln(btfa)₃L], where Ln = La, Eu, Gd or Yb and L= bipy or phen (phen=1,10-phenanthroline) using a combined theoretical-experimental approach. These complexes were synthesized and fully characterized, and detailed NMR measurements were obtained. They were also studied by quantum chemical computational methods (DFT-PBE0). The aim was to determine the relevant factors in the structure of these compounds that favor or not the fluxional behavior. Measurements of the 1H NMR signals at variable temperature in CD₂Cl₂ of the [Eu(btfa)₃L] complexes suggest that these compounds have a fluxional structure, because the crystal structure has non-equivalent btfa ligands that should lead to non-equivalent hydrogen atoms and thus to more signals in the NMR spectra than those obtained at room temperature, where all hydrogen atoms of the btfa ligands are equivalent, and phen ligand has an effective vertical symmetry plane. For the [Eu(btfa)₃bipy] complex, the broadening of the signals at –70°C provides a lower bound for the coalescence temperature, which indicates the energy barriers involved in the structural interconversion mechanisms are quite small. These barriers and, consequently, the coalescence temperature are dependent upon the radii of the lanthanide ion as well as to their paramagnetic effects. The PBE0 calculated structures are in very good agreement with the crystallographic data and, for the [Eu(btfa)₃bipy] complex, this method provided several distinct structures with almost the same energy. However, the energy barrier for structural interconversion via dissociative pathways were found to be quite high and could not explain the experimental observations. Whereas the pseudo-rotation pathways, involving the btfa and bipy ligands, have very small activation barriers, in excellent agreement with the NMR data. The results also showed an increase in the activation barrier along the lanthanide series due to the decrease of the ionic radii and consequent increase of the steric effects. TD-DFT calculations showed a dependence of the ligand donor state energy with different structures of the complex [Eu(btfa)₃phen], which can affect the energy transfer rates and the luminescence. The energy required to promote the structural fluxionality may also enhance the luminescence quenching in solution. These results can aid in the design of more luminescent compounds and more efficient devices.

Keywords: computational chemistry, lanthanide-based compounds, NMR, structural fluxionality

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31 Wave Agitated Signatures in the Oolitic Limestones of Kunihar Formation, Proterozoic Simla Group, Lesser Himalaya, India

Authors: Alono Thorie, Ananya Mukhopadhyay

Abstract:

Ooid bearing horizons of the Proterozoic Kunihar Formation, Simla Group, Lesser Himalaya have been addressed in the present work. The study is concentrated around the outskirts of Arki town, Solan district, Himachal Pradesh, India. Based on the sedimentary facies associations, the processes that promote the formation of ooids have been documented. The facies associations that have been recorded are: (i) Oolitic-Intraclastic grainstone (FA1), (ii) Oolitic grainstone (FA2), (iii) Boundstone (FA3), (iv) Dolomudstone (FA4) and (v) Rudstone (FA5). Oolitic-Intraclastic grainstone (FA1) mainly consists of well sorted ooids with concentric laminae and intraclasts. Large ooids with grain sizes more than 4 mm are characteristic of oolites throughout the area. Normally graded beds consisting of ooids and intraclasts are frequently documented in storm sediments in shelf environments and carbonate platforms. The well-sorted grainstone fabric indicates deposition in a high-energy shoal with tidal currents and storm reworking. FA2 comprises spherical to elliptical grains up to 8.5cm in size with concentric cortex and micritic nuclei. Peloids in FA2 are elliptical, rounded objects <0.3 mm in size. FA1 and FA2 have been recorded alongside boundstones (FA3) comprising stromatolites having columnar, wavy and domal morphology. Boundstones (FA3) reflect microbial growth in carbonate platforms and reefs. Dolomudstones (FA4) interbedded with cross laminated sandstones and erosional surfaces reflect sedimentation in storm dominated zones below fair-weather wave base. Rudstone (FA5) is composed of oolitic grainstone (FA2), boundstone (FA3) and dolomudstone (FA4). These clasts are few mm to more than 10 cm in length. Rudstones indicate deposition along a slope with intermittent influence of wave currents and storm activities. Most ooids from the Kunihar Formation are regular ooids with abundance of broken ooids. Compound and concentric ooids indicating medium to low energy environments are present but scarce. Ooids from high energy domains are more dominant than ooids developed from low energy environments. The unusually large size of the Kunihar ooids (more than 8.5 cm) is rare in the geological record. Development of carbonate deposits such as oolitic- intraclastic Grainstones (FA1), oolitic grainstones (FA2) and rudstones (FA5), and reflect deposition in an agitated beach environment with abundant microbial activity and high energy shallow marine waters influenced by tide, wave and storm currents. Occurrences of boundstone (FA4) or stromatolitic carbonate amongst oolitic facies (FA1 and FA2) and appearance of compound and concentric ooids indicate intervals of calm in between agitated phases of storm, wave and tidal activities.

Keywords: proterozoic, Simla Group, ooids, stromatolites

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30 Mannose-Functionalized Lipopolysaccharide Nanoparticles for Macrophage-Targeted Dual Delivery of Rifampicin and Isoniazid

Authors: Mumuni Sumaila, Viness Pillay, Yahya E. Choonara, Pradeep Kumar, Pierre P. Kondiah

Abstract:

Tuberculosis (TB) remains a serious challenge to public health globally, despite every effort put together to curb the disease. Current TB therapeutics available have proven to be inefficient due to a multitude of drawbacks that range from serious adverse effects/drug toxicity to inconsistent bioavailability, which ultimately contributes to the emergence of drug-resistant TB. An effective ‘cargo’ system designed to cleverly deliver therapeutic doses of anti-TB drugs to infection sites and in a sustained-release manner may provide a better therapeutic choice towards winning the war against TB. In the current study, we investigated mannose-functionalized lipopolysaccharide hybrid nanoparticles for safety and efficacy towards macrophage-targeted simultaneous delivery of the two first-line anti-TB drugs, rifampicin (RF) and isoniazid (IS). RF-IS-loaded lipopolysaccharide hybrid nanoparticles were fabricated using the solvent injection technique (SIT), incorporating soy lecithin (SL) and low molecular weight chitosan (CS) as the lipid and polysaccharide components, respectively. Surface-functionalized nanoparticles were obtained through the reaction of the aldehyde group of mannose with free amine functionality present at the surface of the nanoparticles. The functionalized nanocarriers were spherical with average particle size and surface charge of 107.83 nm and +21.77 mV, respectively, and entrapment efficiencies (EE) were 53.52% and 69.80% for RF and IS, respectively. FTIR spectrum revealed high-intensity bands between 1663 cm⁻¹ and 1408 cm⁻¹ wavenumbers (absent in non-functionalized nanoparticles), which could be attributed to the C=N stretching vibration produced by the formation of Schiff’s base (–N=CH–) during the mannosylation reaction. In vitro release studies showed a sustained-release profile for RF and IS, with less than half of the total payload released over a 48-hour period. The nanocarriers were biocompatible and safe, with more than 80% cell viability achieved when incubated with RAW 264.7 cells at concentrations 30 to 500 μg/mL over a 24-hour period. Cellular uptake studies (after a 24-hour incubation period with the murine macrophage cells, RAW 264.7) revealed a 13- and a 9-fold increase in intracellular accumulation of RF and IS, respectively, when compared with the unformulated RF+IS solution. A 6- and a 3-fold increase in intracellular accumulation of RF and IS, respectively, were observed when compared with the non-functionalized nanoparticles. Furthermore, fluorescent microscopy images showed nanoparticle internalization and accumulation within the RAW 264.7 cells, which was more significant in the mannose-functionalized system compared to the non-functionalized nanoparticles. The overall results suggested that the fabricated mannose-functionalized lipopolysaccharide nanoparticles are a safe and promising platform for macrophage-targeted delivery of anti-TB therapeutics. However, in vivo pharmacokinetic/pharmacodynamics studies are required to further substantiate the therapeutic efficacy of the nanosystem.

Keywords: anti-tuberculosis therapeutics, hybrid nanosystem, lipopolysaccharide nanoparticles, macrophage-targeted delivery

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29 Production, Characterization and In vitro Evaluation of [223Ra]RaCl2 Nanomicelles for Targeted Alpha Therapy of Osteosarcoma

Authors: Yang Yang, Luciana Magalhães Rebelo Alencar, Martha Sahylí Ortega Pijeira, Beatriz da Silva Batista, Alefe Roger Silva França, Erick Rafael Dias Rates, Ruana Cardoso Lima, Sara Gemini-Piperni, Ralph Santos-Oliveira

Abstract:

Radium-²²³ dichloride ([²²³Rₐ]RₐCl₂) is an alpha particle-emitting radiopharmaceutical currently approved for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease. [²²³Rₐ]RₐCl₂ is bone-seeking calcium mimetic that bonds into the newly formed bone stroma, especially osteoblastic or sclerotic metastases, killing the tumor cells by inducing DNA breaks in a potent and localized manner. Nonetheless, the successful therapy of osteosarcoma as primary bone tumors is still a challenge. Nanomicelles are colloidal nanosystems widely used in drug development to improve blood circulation time, bioavailability, and specificity of therapeutic agents, among other applications. In addition, the enhanced permeability and retention effect of the nanosystems, and the renal excretion of the nanomicelles reported in most cases so far, are very attractive to achieve selective and increased accumulation in tumor site as well as to increase the safety of [²²³Rₐ]RₐCl₂ in the clinical routine. In the present work, [²²³Rₐ]RₐCl₂ nanomicelles were produced, characterized, in vitro evaluated, and compared with pure [²²³Rₐ]RₐCl2 solution using SAOS2 osteosarcoma cells. The [²²³Rₐ]RₐCl₂ nanomicelles were prepared using the amphiphilic copolymer Pluronic F127. The dynamic light scattering analysis of freshly produced [²²³Rₐ]RₐCl₂ nanomicelles demonstrated a mean size of 129.4 nm with a polydispersity index (PDI) of 0.303. After one week stored in the refrigerator, the mean size of the [²²³Rₐ]RₐCl₂ nanomicelles increased to 169.4 with a PDI of 0.381. Atomic force microscopy analysis of [223Rₐ]RₐCl₂ nanomicelles exhibited spherical structures whose heights reach 1 µm, suggesting the filling of 127-Pluronic nanomicelles with [²²³Rₐ]RₐCl₂. The viability assay with [²²³Rₐ]RₐCl₂ nanomicelles displayed a dose-dependent response as it was observed using pure [²²³Rₐ]RₐCl2. However, at the same dose, [²²³Rₐ]RₐCl₂ nanomicelles were 20% higher efficient in killing SAOS2 cells when compared with pure [²²³Rₐ]RₐCl₂. These findings demonstrated the effectiveness of the nanosystem validating the application of nanotechnology in targeted alpha therapy with [²²³Ra]RₐCl₂. In addition, the [²²³Rₐ]RaCl₂nanomicelles may be decorated and incorporated with a great variety of agents and compounds (e.g., monoclonal antibodies, aptamers, peptides) to overcome the limited use of [²²³Ra]RₐCl₂.

Keywords: nanomicelles, osteosarcoma, radium dichloride, targeted alpha therapy

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28 Ways to Prevent Increased Wear of the Drive Box Parts and the Central Drive of the Civil Aviation Turbo Engine Based on Tribology

Authors: Liudmila Shabalinskaya, Victor Golovanov, Liudmila Milinis, Sergey Loponos, Alexander Maslov, D. O. Frolov

Abstract:

The work is devoted to the rapid laboratory diagnosis of the condition of aircraft friction units, based on the application of the nondestructive testing method by analyzing the parameters of wear particles, or tribodiagnostics. The most important task of tribodiagnostics is to develop recommendations for the selection of more advanced designs, materials and lubricants based on data on wear processes for increasing the life and ensuring the safety of the operation of machines and mechanisms. The object of tribodiagnostics in this work are the tooth gears of the central drive and the gearboxes of the gas turbine engine of the civil aviation PS-90A type, in which rolling friction and sliding friction with slip occur. The main criterion for evaluating the technical state of lubricated friction units of a gas turbine engine is the intensity and rate of wear of the friction surfaces of the friction unit parts. When the engine is running, oil samples are taken and the state of the friction surfaces is evaluated according to the parameters of the wear particles contained in the oil sample, which carry important and detailed information about the wear processes in the engine transmission units. The parameters carrying this information include the concentration of wear particles and metals in the oil, the dispersion composition, the shape, the size ratio and the number of particles, the state of their surfaces, the presence in the oil of various mechanical impurities of non-metallic origin. Such a morphological analysis of wear particles has been introduced into the order of monitoring the status and diagnostics of various aircraft engines, including a gas turbine engine, since the type of wear characteristic of the central drive and the drive box is surface fatigue wear and the beginning of its development, accompanied by the formation of microcracks, leads to the formation of spherical, up to 10 μm in size, and in the aftermath of flocculent particles measuring 20-200 μm in size. Tribodiagnostics using the morphological analysis of wear particles includes the following techniques: ferrography, filtering, and computer analysis of the classification and counting of wear particles. Based on the analysis of several series of oil samples taken from the drive box of the engine during their operating time, a study was carried out of the processes of wear kinetics. Based on the results of the study and comparing the series of criteria for tribodiagnostics, wear state ratings and statistics of the results of morphological analysis, norms for the normal operating regime were developed. The study allowed to develop levels of wear state for friction surfaces of gearing and a 10-point rating system for estimating the likelihood of the occurrence of an increased wear mode and, accordingly, prevention of engine failures in flight.

Keywords: aviation, box of drives, morphological analysis, tribodiagnostics, tribology, ferrography, filtering, wear particle

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27 The Effect of the Performance Evolution System on the Productivity of Administrating and a Case Study

Authors: Ertuğrul Ferhat Yilmaz, Ali Riza Perçin

Abstract:

In the business enterprises implemented modern business enterprise principles, the most important issues are increasing the performance of workers and getting maximum income. Through the twentieth century, rapid development of the sectors of data processing and communication and because of the free trade politics arising of multilateral business enterprises have canceled the economical borders and changed the local rivalry into the spherical rivalry. In this rivalry conditions, the business enterprises have to work active and productive in order to continue their existences. The employees worked at business enterprises have formed the most important factor of product. Therefore, the business enterprises inferring the importance of the human factors in order to increase the profit have used “the performance evolution system” to increase the success and development of the employees. The evolution of the performance is aimed to increase the manpower productive by using the employees in an active way. Furthermore, this system assists the wage politics implemented in business enterprise, determining the strategically plans in business enterprises through the short and long terms, being promoted and determining the educational needs of employees, making decisions as dismissing and work rotation. It requires a great deal of effort to catch the pace of change in the working realm and to keep up ourselves up-to-date. To get the quality in people,to have an effect in workplace depends largely on the knowledge and competence of managers and prospective managers. Therefore,managers need to use the performance evaluation systems in order to base their managerial decisions on sound data. This study aims at finding whether the organizations effectively use performance evaluation systms,how much importance is put on this issue and how much the results of the evaulations have an effect on employees. Whether the organizations have the advantage of competition and can keep on their activities depend to a large extent on how they effectively and efficiently use their employees.Therefore,it is of vital importance to evaluate employees' performance and to make them better according to the results of that evaluation. The performance evaluation system which evaluates the employees according to the criteria related to that organization has become one of the most important topics for management. By means of those important ends mentioned above,performance evaluation system seems to be a tool that can be used to improve the efficiency and effectiveness of organization. Because of its contribution to organizational success, thinking performance evaluation on the axis of efficiency shows the importance of this study on a different angle. In this study, we have explained performance evaluation system ,efficiency and the relation between those two concepts. We have also analyzed the results of questionnaires conducted on the textile workers in Edirne city.We have got positive answers from the questions about the effects of performance evaluation on efficiency.After factor analysis ,the efficiency and motivation which are determined as factors of performance evaluation system have the biggest variance (%19.703) in our sample. Thus, this study shows that objective performance evaluation increases the efficiency and motivation of employees.

Keywords: performance, performance evolution system, productivity, Edirne region

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26 Thermo-Mechanical Processing Scheme to Obtain Micro-Duplex Structure Favoring Superplasticity in an As-Cast and Homogenized Medium Alloyed Nickel Base Superalloy

Authors: K. Sahithya, I. Balasundar, Pritapant, T. Raghua

Abstract:

Ni-based superalloy with a nominal composition Ni-14% Cr-11% Co-5.8% Mo-2.4% Ti-2.4% Nb-2.8% Al-0.26 % Fe-0.032% Si-0.069% C (all in wt %) is used as turbine discs in a variety of aero engines. Like any other superalloy, the primary processing of the as-cast superalloy poses a major challenge due to its complex alloy chemistry. The challenge was circumvented by characterizing the different phases present in the material, optimizing the homogenization treatment, identifying a suitable thermomechanical processing window using dynamic materials modeling. The as-cast material was subjected to homogenization at 1200°C for a soaking period of 8 hours and quenched using different media. Water quenching (WQ) after homogenization resulted in very fine spherical γꞌ precipitates of sizes 30-50 nm, whereas furnace cooling (FC) after homogenization resulted in bimodal distribution of precipitates (primary gamma prime of size 300nm and secondary gamma prime of size 5-10 nm). MC type primary carbides that are stable till the melting point of the material were found in both WQ and FC samples. Deformation behaviour of both the materials below (1000-1100°C) and above gamma prime solvus (1100-1175°C) was evaluated by subjecting the material to series of compression tests at different constant true strain rates (0.0001/sec-1/sec). An in-detail examination of the precipitate dislocation interaction mechanisms carried out using TEM revealed precipitate shearing and Orowan looping as the mechanisms governing deformation in WQ and FC, respectively. Incoherent/semi coherent gamma prime precipitates in the case of FC material facilitates better workability of the material, whereas the coherent precipitates in WQ material contributed to higher resistance to deformation of the material. Both the materials exhibited discontinuous dynamic recrystallization (DDRX) above gamma prime solvus temperature. The recrystallization kinetics was slower in the case of WQ material. Very fine grain boundary carbides ( ≤ 300 nm) retarded the recrystallisation kinetics in WQ. Coarse carbides (1-5 µm) facilitate particle stimulated nucleation in FC material. The FC material was cogged (primary hot working) 1120˚C, 0.03/sec resulting in significant grain refinement, i.e., from 3000 μm to 100 μm. The primary processed material was subjected to intensive thermomechanical deformation subsequently by reducing the temperature by 50˚C in each processing step with intermittent heterogenization treatment at selected temperatures aimed at simultaneous coarsening of the gamma prime precipitates and refinement of the gamma matrix grains. The heterogeneous annealing treatment carried out, resulted in gamma grains of 10 μm and gamma prime precipitates of 1-2 μm. Further thermo mechanical processing of the material was carried out at 1025˚C to increase the homogeneity of the obtained micro-duplex structure.

Keywords: superalloys, dynamic material modeling, nickel alloys, dynamic recrystallization, superplasticity

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25 Impact of Material Chemistry and Morphology on Attrition Behavior of Excipients during Blending

Authors: Sri Sharath Kulkarni, Pauline Janssen, Alberto Berardi, Bastiaan Dickhoff, Sander van Gessel

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Blending is a common process in the production of pharmaceutical dosage forms where the high shear is used to obtain a homogenous dosage. The shear required can lead to uncontrolled attrition of excipients and affect API’s. This has an impact on the performance of the formulation as this can alter the structure of the mixture. Therefore, it is important to understand the driving mechanisms for attrition. The aim of this study was to increase the fundamental understanding of the attrition behavior of excipients. Attrition behavior of the excipients was evaluated using a high shear blender (Procept Form-8, Zele, Belgium). Twelve pure excipients are tested, with morphologies varying from crystalline (sieved), granulated to spray dried (round to fibrous). Furthermore, materials include lactose, microcrystalline cellulose (MCC), di-calcium phosphate (DCP), and mannitol. The rotational speed of the blender was set at 1370 rpm to have the highest shear with a Froude (Fr) number 9. Varying blending times of 2-10 min were used. Subsequently, after blending, the excipients were analyzed for changes in particle size distribution (PSD). This was determined (n = 3) by dry laser diffraction (Helos/KR, Sympatec, Germany). Attrition was found to be a surface phenomenon which occurs in the first minutes of the high shear blending process. An increase of blending time above 2 mins showed no change in particle size distribution. Material chemistry was identified as a key driver for differences in the attrition behavior between different excipients. This is mainly related to the proneness to fragmentation, which is known to be higher for materials such as DCP and mannitol compared to lactose and MCC. Secondly, morphology also was identified as a driver of the degree of attrition. Granular products consisting of irregular surfaces showed the highest reduction in particle size. This is due to the weak solid bonds created between the primary particles during the granulation process. Granular DCP and mannitol show a reduction of 80-90% in x10(µm) compared to a 20-30% drop for granular lactose (monohydrate and anhydrous). Apart from the granular lactose, all the remaining morphologies of lactose (spray dried-round, sieved-tomahawk, milled) show little change in particle size. Similar observations have been made for spray-dried fibrous MCC. All these morphologies have little irregular or sharp surfaces and thereby are less prone to fragmentation. Therefore, products containing brittle materials such as mannitol and DCP are more prone to fragmentation when exposed to shear. Granular products with irregular surfaces lead to an increase in attrition. While spherical, crystalline, or fibrous morphologies show reduced impact during high shear blending. These changes in size will affect the functionality attributes of the formulation, such as flow, API homogeneity, tableting, formation of dust, etc. Hence it is important for formulators to fully understand the excipients to make the right choices.

Keywords: attrition, blending, continuous manufacturing, excipients, lactose, microcrystalline cellulose, shear

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24 Investigation of Ground Disturbance Caused by Pile Driving: Case Study

Authors: Thayalan Nall, Harry Poulos

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Piling is the most widely used foundation method for heavy structures in poor soil conditions. The geotechnical engineer can choose among a variety of piling methods, but in most cases, driving piles by impact hammer is the most cost-effective alternative. Under unfavourable conditions, driving piles can cause environmental problems, such as noise, ground movements and vibrations, with the risk of ground disturbance leading to potential damage to proposed structures. In one of the project sites in which the authors were involved, three offshore container terminals, namely CT1, CT2 and CT3, were constructed over thick compressible marine mud. The seabed was around 6m deep and the soft clay thickness within the project site varied between 9m and 20m. CT2 and CT3 were connected together and rectangular in shape and were 2600mx800m in size. CT1 was 400m x 800m in size and was located on south opposite of CT2 towards its eastern end. CT1 was constructed first and due to time and environmental limitations, it was supported on a “forest” of large diameter driven piles. CT2 and CT3 are now under construction and are being carried out using a traditional dredging and reclamation approach with ground improvement by surcharging with vertical drains. A few months after the installation of the CT1 piles, a 2600m long sand bund to 2m above mean sea level was constructed along the southern perimeter of CT2 and CT3 to contain the dredged mud that was expected to be pumped. The sand bund was constructed by sand spraying and pumping using a dredging vessel. About 2000m length of the sand bund in the west section was constructed without any major stability issues or any noticeable distress. However, as the sand bund approached the section parallel to CT1, it underwent a series of deep seated failures leading the displaced soft clay materials to heave above the standing water level. The crest of the sand bund was about 100m away from the last row of piles. There were no plausible geological reasons to conclude that the marine mud only across the CT1 region was weaker than over the rest of the site. Hence it was suspected that the pile driving by impact hammer may have caused ground movements and vibrations, leading to generation of excess pore pressures and cyclic softening of the marine mud. This paper investigates the probable cause of failure by reviewing: (1) All ground investigation data within the region; (2) Soil displacement caused by pile driving, using theories similar to spherical cavity expansion; (3) Transfer of stresses and vibrations through the entire system, including vibrations transmitted from the hammer to the pile, and the dynamic properties of the soil; and (4) Generation of excess pore pressure due to ground vibration and resulting cyclic softening. The evidence suggests that the problems encountered at the site were primarily caused by the “side effects” of the pile driving operations.

Keywords: pile driving, ground vibration, excess pore pressure, cyclic softening

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23 Numerical Investigation of the Influence on Buckling Behaviour Due to Different Launching Bearings

Authors: Nadine Maier, Martin Mensinger, Enea Tallushi

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In general, today, two types of launching bearings are used in the construction of large steel and steel concrete composite bridges. These are sliding rockers and systems with hydraulic bearings. The advantages and disadvantages of the respective systems are under discussion. During incremental launching, the center of the webs of the superstructure is not perfectly in line with the center of the launching bearings due to unavoidable tolerances, which may have an influence on the buckling behavior of the web plates. These imperfections are not considered in the current design against plate buckling, according to DIN EN 1993-1-5. It is therefore investigated whether the design rules have to take into account any eccentricities which occur during incremental launching and also if this depends on the respective launching bearing. Therefore, at the Technical University Munich, large-scale buckling tests were carried out on longitudinally stiffened plates under biaxial stresses with the two different types of launching bearings and eccentric load introduction. Based on the experimental results, a numerical model was validated. Currently, we are evaluating different parameters for both types of launching bearings, such as load introduction length, load eccentricity, the distance between longitudinal stiffeners, the position of the rotation point of the spherical bearing, which are used within the hydraulic bearings, web, and flange thickness and imperfections. The imperfection depends on the geometry of the buckling field and whether local or global buckling occurs. This and also the size of the meshing is taken into account in the numerical calculations of the parametric study. As a geometric imperfection, the scaled first buckling mode is applied. A bilinear material curve is used so that a GMNIA analysis is performed to determine the load capacity. Stresses and displacements are evaluated in different directions, and specific stress ratios are determined at the critical points of the plate at the time of the converging load step. To evaluate the load introduction of the transverse load, the transverse stress concentration is plotted on a defined longitudinal section on the web. In the same way, the rotation of the flange is evaluated in order to show the influence of the different degrees of freedom of the launching bearings under eccentric load introduction and to be able to make an assessment for the case, which is relevant in practice. The input and the output are automatized and depend on the given parameters. Thus we are able to adapt our model to different geometric dimensions and load conditions. The programming is done with the help of APDL and a Python code. This allows us to evaluate and compare more parameters faster. Input and output errors are also avoided. It is, therefore, possible to evaluate a large spectrum of parameters in a short time, which allows a practical evaluation of different parameters for buckling behavior. This paper presents the results of the tests as well as the validation and parameterization of the numerical model and shows the first influences on the buckling behavior under eccentric and multi-axial load introduction.

Keywords: buckling behavior, eccentric load introduction, incremental launching, large scale buckling tests, multi axial stress states, parametric numerical modelling

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22 Antimicrobial and Aroma Finishing of Organic Cotton Knits Using Vetiver Oil Microcapsules for Health Care Textiles

Authors: K. J. Sannapapamma, H. Malligawad Lokanath, Sakeena Naikwadi

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Eco-friendly textiles are gaining importance among the consumers and textile manufacturers in the healthcare sector due to increased environmental pollution which leads to several health and environmental hazards. Hence, the research was designed to cultivate and develop the organic cotton knit, to prepare and characterize the Vetiver oil microcapsules for textile finishing and to access the wash durability of finished knits. The cotton SAHANA variety grown under organic production systems was processed and spun into 30 single yarn dyed with four natural colorants (Arecanut slurry, Eucalyptus leaves, Pomegranate rind and Indigo) and eco dyed yarn was further used for development of single jersy knitted fabric. Vetiveria zizanioides is an aromatic grass which is being traditionally used in medicine and perfumery. Vetiver essential oil was used for preparation of microcapsules by interfacial polymerization technique subjected to Gas Chromatography Mass Spectrometry (GCMS), Fourier Transform Infrared Spectroscopy (FTIR), Thermo Gravimetric Analyzer (TGA) and Scanning Electron Microscope (SEM) for characterization of microcapsules. The knitted fabric was finished with vetiver oil microcapsules by exhaust and pad dry cure methods. The finished organic knit was assessed for laundering on antimicrobial efficiency and aroma intensity. GCMS spectral analysis showed that, diethyl phthalate (28%) was the major compound found in vetiver oil followed by isoaromadendrene epoxide (7.72%), beta-vetivenene (6.92%), solavetivone (5.58%), aromadenderene, azulene and khusimol. Bioassay explained that, the vetiver oil and diluted vetiver oil possessed greater zone of inhibition against S. aureus and E. coli than the coconut oil. FTRI spectra of vetiver oil and microcapsules possessed similar peaks viz., C-H, C=C & C꞊O stretching and additionally oil microcapsules possessed the peak of 3331.24 cm-1 at 91.14 transmittance was attributed to N-H stretches. TGA of oil microcapsules revealed that, there was a minimum weight loss (5.835%) recorded at 467.09°C compared to vetiver oil i.e., -3.026% at the temperature of 396.24°C. The shape of the microcapsules was regular and round, some were spherical in shape and few were rounded by small aggregates. Irrespective of methods of application, organic cotton knits finished with microcapsules by pad dry cure method showed maximum zone of inhibition compared to knits finished by exhaust method against S. aureus and E. coli. The antimicrobial activity of the finished samples was subjected to multiple washing which indicated that knits finished with pad dry cure method showed a zone of inhibition even after 20th wash and better aroma retention compared to knits finished with the exhaust method of application. Further, the group of respondents rated that the 5th washed samples had the greater aroma intensity in both the methods than the other samples. Thus, the vetiver microencapsulated organic cotton knits are free from hazardous chemicals and have multi-functional properties that can be suitable for medical and healthcare textiles.

Keywords: exhaust and pad dry cure finishing, interfacial polymerization, organic cotton knits, vetiver oil microcapsules

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21 Synergistic Studies of Liposomes of Clove and Cinnamon Oil in Oral Health Care

Authors: Sandhya Parameswaran, Prajakta Dhuri

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Despite great improvements in health care, the world oral health report states that dental problems still persist, particularly among underprivileged groups in both developing and developed countries. Dental caries and periodontal diseases are identified as the most important oral health problems globally. Acidic foods and beverages can affect natural teeth, and chronic exposure often leads to the development of dental erosion, abrasion, and decay. In recent years, there has been an increased interest toward essential oils. These are secondary metabolites and possess antibacterial, antifungal and antioxidant properties. Essential oils are volatile and chemically unstable in the presence of air, light, moisture and high temperature. Hence many novel methods like a liposomal encapsulation of oils have been introduced to enhance the stability and bioavailability. This research paper focuses on two essential oils, clove and cinnamon oil. Clove oil was obtained from Syzygium aromaticum Linn using clavengers apparatus. It contains eugenol and β caryophyllene. Cinnamon oil, from the barks of Cinnamomum cassia, contains cinnamaldehyde, The objective of the current research was to develop a liposomal carrier system containing clove and cinnamon oil and study their synergistic activity against dental pathogens when formulated as a gel. Methodology: The essential oil were first tested for their antimicrobial activity against dental pathogens, Lactobacillus acidophillus (MTCC No. 10307, MRS broth) and Streptococcus Mutans (MTCC No .890, Brain Heart Infusion agar). The oils were analysed by UV spectroscopy for eugenol and cinnamaldehyde content. Standard eugenol was linear between 5ppm to 25ppm at 282nm and standard cinnamaldehde from 1ppm to 5pmm at 284nm. The concentration of eugenol in clove oil was found to be 62.65 % w/w, and that of cinnamaldehyde was found to be 5.15%s w/w. The oils were then formulated into liposomes. Liposomes were prepared by thin film hydration method using Phospholipid, Cholesterol, and other oils dissolved in a chloroform methanol (3:1) mixture. The organic solvent was evaporated in a rotary evaporator above lipid transition temperature. The film was hydrated with phosphate buffer (pH 5.5).The various batches of liposomes were characterized and compared for their size, loading rate, encapsulation efficiency and morphology. The prepared liposomes when evaluated for entrapment efficiency showed 65% entrapment for clove and 85% for cinnamon oil. They were also tested for their antimicrobial activity against dental pathogens and their synergistic activity studied. Based on the activity and the entrapment efficiency the amount of liposomes required to prepare 1gm of the gel was calculated. The gel was prepared using a simple ointment base and contained 0.56% of cinnamon and clove liposomes. A simultaneous method of analysis for eugenol and cinnamaldehyde.was then developed using HPLC. The prepared gels were then studied for their stability as per ICH guidelines. Conclusion: It was found that liposomes exhibited spherical shaped vesicles and protected the essential oil from degradation. Liposomes, therefore, constitute a suitable system for encapsulation of volatile, unstable essential oil constituents.

Keywords: cinnamon oil, clove oil, dental caries, liposomes

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20 Antimicrobial Nanocompositions Made of Amino Acid Based Biodegradable Polymers

Authors: Nino Kupatadze, Mzevinar Bedinashvili, Tamar Memanishvili, Manana Gurielidze, David Tugushi, Ramaz Katsarava

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Bacteria easily colonize the surfaces of tissues, surgical devices (implants, orthopedics, catheters, etc.), and instruments causing surgical device related infections. Therefore, the battle against bacteria and the prevention of surgical devices from biofilm formation is one of the main challenges of biomedicine today. Our strategy to the solution of this problem consists in using antimicrobial polymeric coatings as effective “shields” to protect surfaces from bacteria’s colonization and biofilm formation. As one of the most promising approaches look be the use of antimicrobial bioerodible polymeric nanocomposites containing silver nanoparticles (AgNPs). We assume that the combination of an erodible polymer with a strong bactericide should put obstacles to bacteria to occupy the surface and to form biofilm. It has to be noted that this kind of nanocomposites are also promising as wound dressing materials to treat infected superficial wounds. Various synthetic and natural polymers were used for creating biocomposites containing AgNPs as both particles' stabilizers and matrices forming elastic films at surfaces. One of the most effective systems to fabricate AgNPs is an ethanol solution of polyvinylpyrrolidone(PVP) with dissolved AgNO3–ethanol serves as a AgNO3 reductant and PVP as AgNPs stabilizer (through the interaction of nanoparticles with nitrogen atom of the amide group). Though PVP is biocompatible and film-forming polymer, it is not a good candidate to design either "biofilm shield" or wound dressing material because of a high solubility in water – though the solubility of PVP provides the desirable release of AgNPs from the matrix, but the coating is easily washable away from the surfaces. More promising as matrices look water insoluble but bioerodible polymers that can provide the release of AgNPs and form long-lasting coatings at the surfaces. For creating bioerodible water-insoluble antimicrobial coatings containing AgNPs, we selected amino acid based biodegradable polymers(AABBPs)–poly(ester amide)s, poly(ester urea)s, their copolymers containing amide and related groups capable to stabilize AgNPs. Among a huge variety of AABBPs reported we selected the polymers soluble in ethanol. For preparing AgNPs containing nanocompositions AABBPs and AgNO3 were dissolved in ethanol and subjected to photochemical reduction using daylight-irradiation. The formation of AgNPs was observed visually by coloring the solutions in brownish-red. The obtained AgNPs were characterized by UV-spectroscopy, transmission electron microscopy(TEM), and dynamic light scattering(DLS). According to the UV and TEM data, the photochemical reduction resulted presumably in spherical AgNPs with rather high contribution of the particles below 10 nm that are known as responsible for the antimicrobial activity. DLS study showed that average size of nanoparticles formed after photo-reduction in ethanol solution ranged within 50 nm. The in vitro antimicrobial activity study of the new nanocomposite material is in progress now.

Keywords: nanocomposites, silver nanoparticles, polymer, biodegradable

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19 Formulation of Lipid-Based Tableted Spray-Congealed Microparticles for Zero Order Release of Vildagliptin

Authors: Hend Ben Tkhayat , Khaled Al Zahabi, Husam Younes

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Introduction: Vildagliptin (VG), a dipeptidyl peptidase-4 inhibitor (DPP-4), was proven to be an active agent for the treatment of type 2 diabetes. VG works by enhancing and prolonging the activity of incretins which improves insulin secretion and decreases glucagon release, therefore lowering blood glucose level. It is usually used with various classes, such as insulin sensitizers or metformin. VG is currently only marketed as an immediate-release tablet that is administered twice daily. In this project, we aim to formulate an extended-release with a zero-order profile tableted lipid microparticles of VG that could be administered once daily ensuring the patient’s convenience. Method: The spray-congealing technique was used to prepare VG microparticles. Compritol® was heated at 10 oC above its melting point and VG was dispersed in the molten carrier using a homogenizer (IKA T25- USA) set at 13000 rpm. VG dispersed in the molten Compritol® was added dropwise to the molten Gelucire® 50/13 and PEG® (400, 6000, and 35000) in different ratios under manual stirring. The molten mixture was homogenized and Carbomer® amount was added. The melt was pumped through the two-fluid nozzle of the Buchi® Spray-Congealer (Buchi B-290, Switzerland) using a Pump drive (Master flex, USA) connected to a silicone tubing wrapped with silicone heating tape heated at the same temperature of the pumped mix. The physicochemical properties of the produced VG-loaded microparticles were characterized using Mastersizer, Scanning Electron Microscope (SEM), Differential Scanning Calorimeter (DSC) and X‐Ray Diffractometer (XRD). VG microparticles were then pressed into tablets using a single punch tablet machine (YDP-12, Minhua pharmaceutical Co. China) and in vitro dissolution study was investigated using Agilent Dissolution Tester (Agilent, USA). The dissolution test was carried out at 37±0.5 °C for 24 hours in three different dissolution media and time phases. The quantitative analysis of VG in samples was realized using a validated High-Pressure Liquid Chromatography (HPLC-UV) method. Results: The microparticles were spherical in shape with narrow distribution and smooth surface. DSC and XRD analyses confirmed the crystallinity of VG that was lost after being incorporated into the amorphous polymers. The total yields of the different formulas were between 70% and 80%. The VG content in the microparticles was found to be between 99% and 106%. The in vitro dissolution study showed that VG was released from the tableted particles in a controlled fashion. The adjustment of the hydrophilic/hydrophobic ratio of excipients, their concentration and the molecular weight of the used carriers resulted in tablets with zero-order kinetics. The Gelucire 50/13®, a hydrophilic polymer was characterized by a time-dependent profile with an important burst effect that was decreased by adding Compritol® as a lipophilic carrier to retard the release of VG which is highly soluble in water. PEG® (400,6000 and 35 000) were used for their gelling effect that led to a constant rate delivery and achieving a zero-order profile. Conclusion: Tableted spray-congealed lipid microparticles for extended-release of VG were successfully prepared and a zero-order profile was achieved.

Keywords: vildagliptin, spray congealing, microparticles, controlled release

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18 Liposome Loaded Polysaccharide Based Hydrogels: Promising Delayed Release Biomaterials

Authors: J. Desbrieres, M. Popa, C. Peptu, S. Bacaita

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Because of their favorable properties (non-toxicity, biodegradability, mucoadhesivity etc.), polysaccharides were studied as biomaterials and as pharmaceutical excipients in drug formulations. These formulations may be produced in a wide variety of forms including hydrogels, hydrogel based particles (or capsules), films etc. In these formulations, the polysaccharide based materials are able to provide local delivery of loaded therapeutic agents but their delivery can be rapid and not easily time-controllable due to, particularly, the burst effect. This leads to a loss in drug efficiency and lifetime. To overcome the consequences of burst effect, systems involving liposomes incorporated into polysaccharide hydrogels may appear as a promising material in tissue engineering, regenerative medicine and drug loading systems. Liposomes are spherical self-closed structures, composed of curved lipid bilayers, which enclose part of the surrounding solvent into their structure. The simplicity of production, their biocompatibility, the size and similar composition of cells, the possibility of size adjustment for specific applications, the ability of hydrophilic or/and hydrophobic drug loading make them a revolutionary tool in nanomedicine and biomedical domain. Drug delivery systems were developed as hydrogels containing chitosan or carboxymethylcellulose (CMC) as polysaccharides and gelatin (GEL) as polypeptide, and phosphatidylcholine or phosphatidylcholine/cholesterol liposomes able to accurately control this delivery, without any burst effect. Hydrogels based on CMC were covalently crosslinked using glutaraldehyde, whereas chitosan based hydrogels were double crosslinked (ionically using sodium tripolyphosphate or sodium sulphate and covalently using glutaraldehyde). It has been proven that the liposome integrity is highly protected during the crosslinking procedure for the formation of the film network. Calcein was used as model active matter for delivery experiments. Multi-Lamellar vesicles (MLV) and Small Uni-Lamellar Vesicles (SUV) were prepared and compared. The liposomes are well distributed throughout the whole area of the film, and the vesicle distribution is equivalent (for both types of liposomes evaluated) on the film surface as well as deeper (100 microns) in the film matrix. An obvious decrease of the burst effect was observed in presence of liposomes as well as a uniform increase of calcein release that continues even at large time scales. Liposomes act as an extra barrier for calcein release. Systems containing MLVs release higher amounts of calcein compared to systems containing SUVs, although these liposomes are more stable in the matrix and diffuse with difficulty. This difference comes from the higher quantity of calcein present within the MLV in relation with their size. Modeling of release kinetics curves was performed and the release of hydrophilic drugs may be described by a multi-scale mechanism characterized by four distinct phases, each of them being characterized by a different kinetics model (Higuchi equation, Korsmeyer-Peppas model etc.). Knowledge of such models will be a very interesting tool for designing new formulations for tissue engineering, regenerative medicine and drug delivery systems.

Keywords: controlled and delayed release, hydrogels, liposomes, polysaccharides

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17 Harnessing Nature's Fury: Hyptis Suaveolens Loaded Bioactive Liposome for Photothermal Therapy of Lung Cancer

Authors: Sajmina Khatun, Monika Pebam, Aravind Kumar Rengan

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Photothermal therapy, a subset of nanomedicine, takes advantage of light-absorbing agents to generate localized heat, selectively eradicating cancer cells. This innovative approach minimizes damage to healthy tissues and offers a promising avenue for targeted cancer treatment. Unlike conventional therapies, photothermal therapy harnesses the power of light to combat malignancies precisely and effectively, showcasing its potential to revolutionize cancer treatment paradigms. The combined strengths of nanomedicine and photothermal therapy signify a transformative shift toward more effective, targeted, and tolerable cancer treatments in the medical landscape. Utilizing natural products becomes instrumental in formulating diverse bioactive medications owing to their various pharmacological properties attributed to the existence of phenolic structures, triterpenoids, and similar compounds. Hyptis suaveolens, commonly known as pignut, stands as an aromatic herb within the Lamiaceae family and represents a valuable therapeutic plant. Flourishing in swamps and alongside tropical and subtropical roadsides, these noxious weeds impede the development of adjacent plants. Hyptis suaveolens ranks among the most globally distributed alien invasive species. The present investigation revealed that a versatile, biodegradable liposome nanosystem (HIL NPs), incorporating bioactive molecules from Hyptis suaveolens, exhibits effective bioavailability to cancer cells, enabling tumor ablation upon near-infrared (NIR) laser exposure. The components within the nanosystem, specifically the bioactive molecules from Hyptis, function as anticancer agents, aiding in the photothermal ablation of highly metastatic lung cancer cells. Despite being a prolific weed impeding neighboring plant growth, Hyptis suaveolens showcases therapeutic benefits through its bioactive compounds. The obtained HIL NPs, characterized as a photothermally active liposome nanosystem, demonstrate a pronounced fluorescence absorption peak in the NIR range and achieve a high photothermal conversion efficiency under NIR laser irradiation. Transmission electron microscopy (TEM) and particle size analysis reveal that HIL NPs possess a spherical shape with a size of 141 ± 30 nm. Moreover, in vitro assessments of HIL NPs against lung cancer cell lines (A549) indicate effective anticancer activity through a combined cytotoxic effect and hyperthermia. Tumor ablation is facilitated by apoptosis induced by the overexpression of ɣ-H2AX, arresting cancer cell proliferation. Consequently, the multifunctional and biodegradable nanosystem (HIL NPs), incorporating bioactive compounds from Hyptis, provides valuable perspectives for developing an innovative therapeutic strategy originating from a challenging weed. This approach holds promise for potential applications in both bioimaging and the combined use of phyto-photothermal therapy for cancer treatment.

Keywords: bioactive liposome, hyptis suaveolens, photothermal therapy, lung cancer

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16 Potential of Polyphenols from Tamarix Gallica towards Common Pathological Features of Diabetes and Alzheimer’s Diseases

Authors: Asma Ben Hmidene, Mizuho Hanaki, Kazuma Murakami, Kazuhiro Irie, Hiroko Isoda, Hideyuki Shigemori

Abstract:

Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are characterized as a peripheral metabolic disorder and a degenerative disease of the central nervous system, respectively. It is now widely recognized that T2DM and AD share many pathophysiological features including glucose metabolism, increased oxidative stress and amyloid aggregation. Amyloid beta (Aβ) is the components of the amyloid deposits in the AD brain and while the component of the amyloidogenic peptide deposit in the pancreatic islets of Langerhans is identified as human islet amyloid polypeptide (hIAPP). These two proteins are originated from the amyloid precursor protein and have a high sequence similarity. Although the amino acid sequences of amyloidogenic proteins are diverse, they all adopt a similar structure in aggregates called cross-beta-spine. Add at that, extensive studies in the past years have found that like Aβ1-42, IAPP forms early intermediate assemblies as spherical oligomers, implicating that these oligomers possess a common folding pattern or conformation. These similarities can be used in the search for effective pharmacotherapy for DM, since potent therapeutic agents such as antioxidants with a catechol moiety, proved to inhibit Aβ aggregation, may play a key role in the inhibit the aggregation of hIAPP treatment of patients with DM. Tamarix gallica is one of the halophyte species having a powerful antioxidant system. Although it was traditionally used for the treatment of various liver metabolic disorders, there is no report about the use of this plant for the treatment or prevention of T2DM and AD. Therefore, the aim of this work is to investigate their protective effect towards T2DM and AD by isolation and identification of α-glucosidase inhibitors, with antioxidant potential, that play an important role in the glucose metabolism in diabetic patient, as well as, the polymerization of hIAPP and Aβ aggregation inhibitors. Structure-activity relationship study was conducted for both assays. And as for α-glucosidase inhibitors, their mechanism of action and their synergistic potential when applied with a very low concentration of acarbose were also suggesting that they can be used not only as α-glucosidase inhibitors but also be combined with established α-glucosidase inhibitors to reduce their adverse effect. The antioxidant potential of the purified substances was evaluated by DPPH and SOD assays. Th-T assay using 42-mer amyloid β-protein (Aβ42) for AD and hIAPP which is a 37-residue peptide secreted by the pancreatic β –cells for T2DM and Transmission electronic microscopy (TEM) were conducted to evaluate the amyloid aggragation of the actives substances. For α-glucosidase, p-NPG and glucose oxidase assays were performed for determining the inhibition potential and structure-activity relationship study. The Enzyme kinetic protocol was used to study the mechanism of action. From this research, it was concluded that polyphenols playing a role in the glucose metabolism and oxidative stress can also inhibit the amyloid aggregation, and that substances with a catechol and glucuronide moieties inhibiting amyloid-β aggregation, might be used to inhibit the aggregation of hIAPP.

Keywords: α-glucosidase inhibitors, amyloid aggregation inhibition, mechanism of action, polyphenols, structure activity relationship, synergistic potential, tamarix gallica

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15 Characterizing the Rectification Process for Designing Scoliosis Braces: Towards Digital Brace Design

Authors: Inigo Sanz-Pena, Shanika Arachchi, Dilani Dhammika, Sanjaya Mallikarachchi, Jeewantha S. Bandula, Alison H. McGregor, Nicolas Newell

Abstract:

The use of orthotic braces for adolescent idiopathic scoliosis (AIS) patients is the most common non-surgical treatment to prevent deformity progression. The traditional method to create an orthotic brace involves casting the patient’s torso to obtain a representative geometry, which is then rectified by an orthotist to the desired geometry of the brace. Recent improvements in 3D scanning technologies, rectification software, CNC, and additive manufacturing processes have given the possibility to compliment, or in some cases, replace manual methods with digital approaches. However, the rectification process remains dependent on the orthotist’s skills. Therefore, the rectification process needs to be carefully characterized to ensure that braces designed through a digital workflow are as efficient as those created using a manual process. The aim of this study is to compare 3D scans of patients with AIS against 3D scans of both pre- and post-rectified casts that have been manually shaped by an orthotist. Six AIS patients were recruited from the Ragama Rehabilitation Clinic, Colombo, Sri Lanka. All patients were between 10 and 15 years old, were skeletally immature (Risser grade 0-3), and had Cobb angles between 20-45°. Seven spherical markers were placed at key anatomical locations on each patient’s torso and on the pre- and post-rectified molds so that distances could be reliably measured. 3D scans were obtained of 1) the patient’s torso and pelvis, 2) the patient’s pre-rectification plaster mold, and 3) the patient’s post-rectification plaster mold using a Structure Sensor Mark II 3D scanner (Occipital Inc., USA). 3D stick body models were created for each scan to represent the distances between anatomical landmarks. The 3D stick models were used to analyze the changes in position and orientation of the anatomical landmarks between scans using Blender open-source software. 3D Surface deviation maps represented volume differences between the scans using CloudCompare open-source software. The 3D stick body models showed changes in the position and orientation of thorax anatomical landmarks between the patient and the post-rectification scans for all patients. Anatomical landmark position and volume differences were seen between 3D scans of the patient’s torsos and the pre-rectified molds. Between the pre- and post-rectified molds, material removal was consistently seen on the anterior side of the thorax and the lateral areas below the ribcage. Volume differences were seen in areas where the orthotist planned to place pressure pads (usually at the trochanter on the side to which the lumbar curve was tilted (trochanter pad), at the lumbar apical vertebra (lumbar pad), on the rib connected to the apical vertebrae at the mid-axillary line (thoracic pad), and on the ribs corresponding to the upper thoracic vertebra (axillary extension pad)). The rectification process requires the skill and experience of an orthotist; however, this study demonstrates that the brace shape, location, and volume of material removed from the pre-rectification mold can be characterized and quantified. Results from this study can be fed into software that can accelerate the brace design process and make steps towards the automated digital rectification process.

Keywords: additive manufacturing, orthotics, scoliosis brace design, sculpting software, spinal deformity

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14 Study on Aerosol Behavior in Piping Assembly under Varying Flow Conditions

Authors: Anubhav Kumar Dwivedi, Arshad Khan, S. N. Tripathi, Manish Joshi, Gaurav Mishra, Dinesh Nath, Naveen Tiwari, B. K. Sapra

Abstract:

In a nuclear reactor accident scenario, a large number of fission products may release to the piping system of the primary heat transport. The released fission products, mostly in the form of the aerosol, get deposited on the inner surface of the piping system mainly due to gravitational settling and thermophoretic deposition. The removal processes in the complex piping system are controlled to a large extent by the thermal-hydraulic conditions like temperature, pressure, and flow rates. These parameters generally vary with time and therefore must be carefully monitored to predict the aerosol behavior in the piping system. The removal process of aerosol depends on the size of particles that determines how many particles get deposit or travel across the bends and reach to the other end of the piping system. The released aerosol gets deposited onto the inner surface of the piping system by various mechanisms like gravitational settling, Brownian diffusion, thermophoretic deposition, and by other deposition mechanisms. To quantify the correct estimate of deposition, the identification and understanding of the aforementioned deposition mechanisms are of great importance. These mechanisms are significantly affected by different flow and thermodynamic conditions. Thermophoresis also plays a significant role in particle deposition. In the present study, a series of experiments were performed in the piping system of the National Aerosol Test Facility (NATF), BARC using metal aerosols (zinc) in dry environments to study the spatial distribution of particles mass and number concentration, and their depletion due to various removal mechanisms in the piping system. The experiments were performed at two different carrier gas flow rates. The commercial CFD software FLUENT is used to determine the distribution of temperature, velocity, pressure, and turbulence quantities in the piping system. In addition to the in-built models for turbulence, heat transfer and flow in the commercial CFD code (FLUENT), a new sub-model PBM (population balance model) is used to describe the coagulation process and to compute the number concentration along with the size distribution at different sections of the piping. In the sub-model coagulation kernels are incorporated through user-defined function (UDF). The experimental results are compared with the CFD modeled results. It is found that most of the Zn particles (more than 35 %) deposit near the inlet of the plenum chamber and a low deposition is obtained in piping sections. The MMAD decreases along the length of the test assembly, which shows that large particles get deposited or removed in the course of flow, and only fine particles travel to the end of the piping system. The effect of a bend is also observed, and it is found that the relative loss in mass concentration at bends is more in case of a high flow rate. The simulation results show that the thermophoresis and depositional effects are more dominating for the small and larger sizes as compared to the intermediate particles size. Both SEM and XRD analysis of the collected samples show the samples are highly agglomerated non-spherical and composed mainly of ZnO. The coupled model framed in this work could be used as an important tool for predicting size distribution and concentration of some other aerosol released during a reactor accident scenario.

Keywords: aerosol, CFD, deposition, coagulation

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13 Wideband Performance Analysis of C-FDTD Based Algorithms in the Discretization Impoverishment of a Curved Surface

Authors: Lucas L. L. Fortes, Sandro T. M. Gonçalves

Abstract:

In this work, it is analyzed the wideband performance with the mesh discretization impoverishment of the Conformal Finite Difference Time-Domain (C-FDTD) approaches developed by Raj Mittra, Supriyo Dey and Wenhua Yu for the Finite Difference Time-Domain (FDTD) method. These approaches are a simple and efficient way to optimize the scattering simulation of curved surfaces for Dielectric and Perfect Electric Conducting (PEC) structures in the FDTD method, since curved surfaces require dense meshes to reduce the error introduced due to the surface staircasing. Defined, on this work, as D-FDTD-Diel and D-FDTD-PEC, these approaches are well-known in the literature, but the improvement upon their application is not quantified broadly regarding wide frequency bands and poorly discretized meshes. Both approaches bring improvement of the accuracy of the simulation without requiring dense meshes, also making it possible to explore poorly discretized meshes which bring a reduction in simulation time and the computational expense while retaining a desired accuracy. However, their applications present limitations regarding the mesh impoverishment and the frequency range desired. Therefore, the goal of this work is to explore the approaches regarding both the wideband and mesh impoverishment performance to bring a wider insight over these aspects in FDTD applications. The D-FDTD-Diel approach consists in modifying the electric field update in the cells intersected by the dielectric surface, taking into account the amount of dielectric material within the mesh cells edges. By taking into account the intersections, the D-FDTD-Diel provides accuracy improvement at the cost of computational preprocessing, which is a fair trade-off, since the update modification is quite simple. Likewise, the D-FDTD-PEC approach consists in modifying the magnetic field update, taking into account the PEC curved surface intersections within the mesh cells and, considering a PEC structure in vacuum, the air portion that fills the intersected cells when updating the magnetic fields values. Also likewise to D-FDTD-Diel, the D-FDTD-PEC provides a better accuracy at the cost of computational preprocessing, although with a drawback of having to meet stability criterion requirements. The algorithms are formulated and applied to a PEC and a dielectric spherical scattering surface with meshes presenting different levels of discretization, with Polytetrafluoroethylene (PTFE) as the dielectric, being a very common material in coaxial cables and connectors for radiofrequency (RF) and wideband application. The accuracy of the algorithms is quantified, showing the approaches wideband performance drop along with the mesh impoverishment. The benefits in computational efficiency, simulation time and accuracy are also shown and discussed, according to the frequency range desired, showing that poorly discretized mesh FDTD simulations can be exploited more efficiently, retaining the desired accuracy. The results obtained provided a broader insight over the limitations in the application of the C-FDTD approaches in poorly discretized and wide frequency band simulations for Dielectric and PEC curved surfaces, which are not clearly defined or detailed in the literature and are, therefore, a novelty. These approaches are also expected to be applied in the modeling of curved RF components for wideband and high-speed communication devices in future works.

Keywords: accuracy, computational efficiency, finite difference time-domain, mesh impoverishment

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12 Nanocomposite Effect Based on Silver Nanoparticles and Anemposis Californica Extract as Skin Restorer

Authors: Maria Zulema Morquecho Vega, Fabiola CarolinaMiranda Castro, Rafael Verdugo Miranda, Ignacio Yocupicio Villegas, Ana lidia Barron Raygoza, Martin enrique MArquez Cordova, Jose Alberto Duarte Moller

Abstract:

Background: Anemopsis californica, also called (tame grass) belongs to the Saururaceae family small, green plant. The blade is long and wide. Gives a white flower. The plant population is only found in humid, swampy habitats, it grows where there is water, along the banks of streams and water holes. In the winter, it dries up. The leaves, rhizomes, or roots of this plant have been used to treat a range of diseases. Some of its healing properties are used to treat wounds, cold and flu symptoms, spasmodic cough, infection, pain and inflammation, burns, swollen feet, as well as lung ailments, asthma, circulatory problems (varicose veins), rheumatoid arthritis, purifies blood, helps in urinary and digestive tract diseases, sores and healing, for headache, sore throat, diarrhea, kidney pain. The tea made from the leaves and roots is used to treat uterine cancer, womb cancer, relieves menstrual pain and stops excessive bleeding after childbirth. It is also used as a gynecological treatment for infections, hemorrhoids, candidiasis and vaginitis. Objective: To study the cytotoxicity of gels prepared with silver nanoparticles in AC extract combined with chitosan, collagen and hyaluronic acid as an alternative therapy for skin conditions. Methods: The Ag NPs were synthesized according to the following method. A 0.3 mg/mL solution is prepared in 10 ml of deionized water, adjust to pH 12 with NaOH, stirring is maintained constant magnetic and a temperature of 80 °C. Subsequently, 100 ul of a 0.1 M AgNO3 solution and kept stirring constantly for 15 min. Once the reaction is complete, measurements are performed by UV-Vis. A gel was prepared in a 5% solution of acetic acid with the respective nanoparticles and AC extract of silver in the extract of AC. Chitosan is added until the process begins to occur gel. At that time, collagen will be added in a ratio of 3 to 5 drops, and later, hyaluronic acid in 2% of the total compound formed. Finally, after resting for 24 hours, the cytotoxic effect of the gels was studied. in the presence of highly positive bacteria Staphylococcus aureus and highly negative for Escherichia coli. Cultures will be incubated for 24 hours in the presence of the compound and compared with the reference. Results: Silver nanoparticles obtained had a spherical shape and sizes among 20 and 30 nm. UV-Vis spectra confirm the presence of silver nanoparticles showing a surface plasmon around 420 nm. Finally, the test in presence of bacteria yield a good antibacterial property of this nanocompound and tests in people were successful. Conclusion: Gel prepared by biogenic synthesis shown beneficious effects in severe acne, acne vulgaris and wound healing with diabetic patients.

Keywords: anemopsis californica, nanomedicina, biotechnology, biomedicine

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11 Formulation of a Submicron Delivery System including a Platelet Lysate to Be Administered in Damaged Skin

Authors: Sergio A. Bernal-Chavez, Sergio Alcalá-Alcalá, Doris A. Cerecedo-Mercado, Adriana Ganem-Rondero

Abstract:

The prevalence of people with chronic wounds has increased dramatically by many factors including smoking, obesity and chronic diseases, such as diabetes, that can slow the healing process and increase the risk of becoming chronic. Because of this situation, the improvement of chronic wound treatments is a necessity, which has led to the scientific community to focus on improving the effectiveness of current therapies and the development of new treatments. The wound formation is a physiological complex process, which is characterized by an inflammatory stage with the presence of proinflammatory cells that create a proteolytic microenvironment during the healing process, which includes the degradation of important growth factors and cytokines. This decrease of growth factors and cytokines provides an interesting strategy for wound healing if they are administered externally. The use of nanometric drug delivery systems, such as polymer nanoparticles (NP), also offers an interesting alternative around dermal systems. An interesting strategy would be to propose a formulation based on a thermosensitive hydrogel loaded with polymeric nanoparticles that allows the inclusion and application of a platelet lysate (PL) on damaged skin, with the aim of promoting wound healing. In this work, NP were prepared by a double emulsion-solvent evaporation technique, using polylactic-co-glycolic acid (PLGA) as biodegradable polymer. Firstly, an aqueous solution of PL was emulsified into a PLGA organic solution, previously prepared in dichloromethane (DCM). Then, this disperse system (W/O) was poured into a polyvinyl alcohol (PVA) solution to get the double emulsion (W/O/W), finally the DCM was evaporated by magnetic stirring resulting in the NP formation containing PL. Once the NP were obtained, these systems were characterized by morphology, particle size, Z-potential, encapsulation efficiency (%EE), physical stability, infrared spectrum, calorimetric studies (DSC) and in vitro release profile. The optimized nanoparticles were included in a thermosensitive gel formulation of Pluronic® F-127. The gel was prepared by the cold method at 4 °C and 20% of polymer concentration. Viscosity, sol-gel phase transition, time of no flow solid-gel at wound temperature, changes in particle size by temperature-effect using dynamic light scattering (DLS), occlusive effect, gel degradation, infrared spectrum and micellar point by DSC were evaluated in all gel formulations. PLGA NP of 267 ± 10.5 nm and Z-potential of -29.1 ± 1 mV were obtained. TEM micrographs verified the size of NP and evidenced their spherical shape. The %EE for the system was around 99%. Thermograms and in infrared spectra mark the presence of PL in NP. The systems did not show significant changes in the parameters mentioned above, during the stability studies. Regarding the gel formulation, the transition sol-gel occurred at 28 °C with a time of no flow solid-gel of 7 min at 33°C (common wound temperature). Calorimetric, DLS and infrared studies corroborated the physical properties of a thermosensitive gel, such as the micellar point. In conclusion, the thermosensitive gel described in this work, contains therapeutic amounts of PL and fulfills the technological properties to be used in damaged skin, with potential application in wound healing and tissue regeneration.

Keywords: growth factors, polymeric nanoparticles, thermosensitive hydrogels, tissue regeneration

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10 Multifield Problems in 3D Structural Analysis of Advanced Composite Plates and Shells

Authors: Salvatore Brischetto, Domenico Cesare

Abstract:

Major improvements in future aircraft and spacecraft could be those dependent on an increasing use of conventional and unconventional multilayered structures embedding composite materials, functionally graded materials, piezoelectric or piezomagnetic materials, and soft foam or honeycomb cores. Layers made of such materials can be combined in different ways to obtain structures that are able to fulfill several structural requirements. The next generation of aircraft and spacecraft will be manufactured as multilayered structures under the action of a combination of two or more physical fields. In multifield problems for multilayered structures, several physical fields (thermal, hygroscopic, electric and magnetic ones) interact each other with different levels of influence and importance. An exact 3D shell model is here proposed for these types of analyses. This model is based on a coupled system including 3D equilibrium equations, 3D Fourier heat conduction equation, 3D Fick diffusion equation and electric and magnetic divergence equations. The set of partial differential equations of second order in z is written using a mixed curvilinear orthogonal reference system valid for spherical and cylindrical shell panels, cylinders and plates. The order of partial differential equations is reduced to the first one thanks to the redoubling of the number of variables. The solution in the thickness z direction is obtained by means of the exponential matrix method and the correct imposition of interlaminar continuity conditions in terms of displacements, transverse stresses, electric and magnetic potentials, temperature, moisture content and transverse normal multifield fluxes. The investigated structures have simply supported sides in order to obtain a closed form solution in the in-plane directions. Moreover, a layerwise approach is proposed which allows a 3D correct description of multilayered anisotropic structures subjected to field loads. Several results will be proposed in tabular and graphical formto evaluate displacements, stresses and strains when mechanical loads, temperature gradients, moisture content gradients, electric potentials and magnetic potentials are applied at the external surfaces of the structures in steady-state conditions. In the case of inclusions of piezoelectric and piezomagnetic layers in the multilayered structures, so called smart structures are obtained. In this case, a free vibration analysis in open and closed circuit configurations and a static analysis for sensor and actuator applications will be proposed. The proposed results will be useful to better understand the physical and structural behaviour of multilayered advanced composite structures in the case of multifield interactions. Moreover, these analytical results could be used as reference solutions for those scientists interested in the development of 3D and 2D numerical shell/plate models based, for example, on the finite element approach or on the differential quadrature methodology. The correct impositions of boundary geometrical and load conditions, interlaminar continuity conditions and the zigzag behaviour description due to transverse anisotropy will be also discussed and verified.

Keywords: composite structures, 3D shell model, stress analysis, multifield loads, exponential matrix method, layer wise approach

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9 Obstructive Bronchitis and Pneumonia by a Mixed Infection of HPIV- 3, S. pneumoniae in an Immunocompromised 10M Infant: Case Report

Authors: Olga Smilevska Spasova, Katerina Boshkovska, Gorica Popova, Mirjana Popovska

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Introduction: Pneumonia is an infection of the pulmonary parenchyma. HPIV 3 is one of four viruses that is a member of the Paramyxoviridae family designated types 1-4 that have a nonsegmented, single-stranded RNA genome with a lipid-containing envelope. They are spread from the respiratory tract by aerosolized secretions or by direct contact with secretions. Type 3 is endemic and can cause serious illness in immunocompromised patients. Illness caused by parainfluenza occurs shortly after inoculation with the virus. The level of immunoglobulin A antibody in serum is the best predictor of susceptibility to infection. Streptococcus pneumonia or pneumococcus is a Gram-positive, spherical bacteria, usually found in pairs and it is a member of the genus Streptococcus. Streptococcus pneumonia resides asymptomatically in healthy carriers typically colonizing the respiratory tract, sinuses, and nasal cavity. In individuals with weaker immune systems like young infants, pneumococcal bacterium is the most common cause of community-acquired pneumonia in the world. Case Report: The aim is to present a case of lower respiratory tract infection in an infant caused by parainfluenza virus 3, S. pneumonia and undifferentiated gram-negative bacteria that was successfully treated. The infant is with a history of recurrent episodes of wheezing in the past 3mounts.Infant of 10months presents 2weeks before admittance with high fever, runny nose, and cough. The primary pediatrician prescribed oral cefpodoxime for 10days and inhaled salbutamol. Two days before admittance in hospital the infant with high fever, cough, and difficulty breathing. At admittance, infant is pale, anxious with rapid respirations, cough, wheezing and tachycardia. On auscultation: vesicular breathing sounds with high pitched wheezing and on the right coarse crackles. Investigations: Blood analysis: RBC: 4, 7 x1012L, WBC: 8,3x109L: Neut: 42.73% Lym: 41.57%, Hgb: 9.38 g/dl MCV: 62.7fl, MCH: 20.0pg MCHC: 31.8 g/dl RDW: 18.7% Plt-307.9 x109LCRP: 2,5mg/l, serum iron-7.92umol/l, O2sat-97% on blood gas analysis, puls-125/min.X-ray of chest with hyperinflationand right pericardial consolidation. Microbiological analysis of sputum sample is positive for undifferentiated gram-negative bacteria (colonizer)–resistant to cefotaxime, ampicillin, cefoxitin, sulfamet.+trimetoprim and sensitive to amikacin, gentamicin, and ciprofloxacin. Molecular multiplex RT-PCR for 19 viruses and multiplex PCR for 7 bacteria test for respiratory pathogens positive for Parainfluenza virus 3(Ct=22.73), Streptococcus pneumonia (Ct=26.75).IED: IgG-9.31g/l, IgA-0.351g/l, IgM-0.86g/l. Therapy: Treatment was started with inhaled salbutamol, intravenous antibiotic cefotaxime as well as systemic corticosteroids. On day 7 because of slow clinical resolution of chest auscultation findings and an etiologic clue with a positive sputum sample for resistant undifferentiated gram negative bacteria, a second intravenous antibiotic was administered amikacin. The infant is discharged on day 14 with resolution of clinical findings. Conclusion: Mixed co-infections with respiratory viruses and bacteria in immunocompromised infants are likely to lead to a more severe form of community acquired pneumonia that will need hospitalization.

Keywords: HPIV- 3, infant, pneumonia, S. pneumonia, x-ray chest

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8 Azadirachta indica Derived Protein Encapsulated Novel Guar Gum Nanocapsules against Colon Cancer

Authors: Suman Chaudhary, Rupinder K. Kanwar, Jagat R. Kanwar

Abstract:

Azadirachta indica, also known as Neem belonging to the mahogany family is actively gaining interest in the era of modern day medicine due to its extensive applications in homeopathic medicine such as Ayurveda and Unani. More than 140 phytochemicals have been extracted from neem leaves, seed, bark and flowers for agro-medicinal applications. Among the various components, neem leaf protein (NLP) is currently the most investigated active ingredient, due to its immunomodulatory activities against tumor growth. However, these therapeutic ingredients of neem are susceptible to degradation and cannot withstand the drastic pH changes under physiological environment, and therefore, there is an urgent need of an alternative strategy such as a nano-delivery system to exploit its medicinal benefits. This study hypothesizes that guar gum (GG) derived biodegradable nano-carrier based encapsulation of NLP will improve its stability, specificity and sensitivity, thus facilitating targeted anti-cancer therapeutics. GG is a galactomannan derived from the endosperm of the guar beans seeds. Synthesis of guar nanocapsules (NCs) was performed using nanoprecipitation technique where the GG was encapsulated with NLP. Preliminary experiments conducted to characterize the NCs confirmed spherical morphology with a narrow size distribution of 30-40 nm. Differential scanning colorimetric analysis (DSC) validated the stability of these NCs even at a temperature range of 50-60°C which was well within the physiological and storage conditions. Thermogravimetric (TGA) analysis indicated high decomposition temperature of these NCs ranging upto 350°C. Additionally, Fourier Transform Infrared spectroscopy (FTIR) and the SDS-PAGE data acquired confirmed the successful encapsulation of NLP in the NCs. The anti-cancerous therapeutic property of this NC was tested on colon cancer cells (caco-2) as they are one of the most prevalent form of cancer. These NCs (both NLP loaded and void) were also tested on human intestinal epithelial cells (FHs 74) cells to evaluate their effect on normal cells. Cytotoxicity evaluation of the NCs in the cell lines confirmed that the IC50 for NLP in FHs 74 cells was ~2 fold higher than in caco-2 cells, indicating that this nanoformulation system possessed biocompatible anti-cancerous properties Immunoconfocal microscopy analysis confirmed the time dependent internalization of the NCs within 6h. Recent findings performed using Annexin V and PI staining indicated a significant increase (p ≤ 0.001) in the early and late apoptotic cell population when treated with the NCs signifying the role of NLP in inducing apoptosis in caco-2 cells. This was further validated using Western blot, Polymerase chain reaction (PCR) and Fluorescence activated cell sorter (FACS) aided protein expressional analysis which presented a downregulation of survivin, an anti-apoptotic cell marker and upregulation of Bax/Bcl-2 ratio (pro-apoptotic indicator). Further, both the NLP NC and unencapsulated NLP treatment destabilized the mitochondrial membrane potential subsequently facilitating the release of the pro-apoptotic caspase cascade initiator, cytochrome-c. Future studies will be focused towards granting specificity to these NCs towards cancer cells, along with a comprehensive analysis of the anti-cancer potential of this naturally occurring compound in different cancer and in vivo animal models, will validate the clinical application of this unprecedented protein therapeutic.

Keywords: anti-tumor, guar gum, nanocapsules, neem leaf protein

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