Search results for: time of release
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 18500

Search results for: time of release

18320 The Comparison of Chromium Ions Release Stainless Steel 18-8 between Artificial Saliva and Black Tea Leaves Extracts

Authors: Nety Trisnawaty, Mirna Febriani

Abstract:

The use of stainless steel wires in the field of dentistry is widely used, especially for orthodontic and prosthodontic treatment using stainless steel wire. The oral cavity is the ideal environment for corrosion, which can be caused by saliva. Prevention of corrosion on stainless steel wires can be done by using an organic or non-organic corrosion inhibitor. One of the organic inhibitors that can be used to prevent corrosion is black tea leaves extracts. To explain the comparison of chromium ions release for stainlees steel between artificial saliva and black tea leaves extracts. In this research we used artificial saliva, black tea leaves extracts, stainless steel wire and using Atomic Absorption Spectrophometric testing machine. The samples were soaked for 1, 3, 7 and 14 days in the artificial saliva and black tea leaves extracts. The results showed the difference of chromium ion release soaked in artificial saliva and black tea leaves extracts on days 1, 3, 7 and 14. Statistically, calculation with independent T-test with p < 0,05 showed a significant difference. The longer the duration of days, the more ion chromium were released. The conclusion of this study shows that black tea leaves extracts can inhibit the corrosion rate of stainless steel wires.

Keywords: chromium ion, stainless steel, artificial saliva, black tea leaves extracts

Procedia PDF Downloads 245
18319 Effects of Nitrogen Addition on Litter Decomposition and Nutrient Release in a Temperate Grassland in Northern China

Authors: Lili Yang, Jirui Gong, Qinpu Luo, Min Liu, Bo Yang, Zihe Zhang

Abstract:

Anthropogenic activities have increased nitrogen (N) inputs to grassland ecosystems. Knowledge of the impact of N addition on litter decomposition is critical to understand ecosystem carbon cycling and their responses to global climate change. The aim of this study was to investigate the effects of N addition and litter types on litter decomposition of a semi-arid temperate grassland during growing and non-growing seasons in Inner Mongolia, northern China, and to identify the relation between litter decomposition and C: N: P stoichiometry in the litter-soil continuum. Six levels of N addition were conducted: CK, N1 (0 g Nm−2 yr−1), N2 (2 g Nm−2 yr−1), N3 (5 g Nm−2 yr−1), N4 (10 g Nm−2 yr−1) and N5 (25 g Nm−2 yr−1). Litter decomposition rates and nutrient release differed greatly among N addition gradients and litter types. N addition promoted litter decomposition of S. grandis, but exhibited no significant influence on L. chinensis litter, indicating that the S. grandis litter decomposition was more sensitive to N addition than L. chinensis. The critical threshold for N addition to promote mixed litter decomposition was 10 -25g Nm−2 yr−1. N addition altered the balance of C: N: P stoichiometry between litter, soil and microbial biomass. During decomposition progress, the L. chinensis litter N: P was higher in N2-N4 plots compared to CK, while the S. grandis litter C: N was lower in N3 and N4 plots, indicating that litter N or P content doesn’t satisfy microbial decomposers with the increasing of N addition. As a result, S. grandis litter exhibited net N immobilization, while L. chinensis litter net P immobilization. Mixed litter C: N: P stoichiometry satisfied the demand of microbial decomposers, showed net mineralization during the decomposition process. With the increasing N deposition in the future, mixed litter would potentially promote C and nutrient cycling in grassland ecosystem by increasing litter decomposition and nutrient release.

Keywords: C: N: P stoichiometry, litter decomposition, nitrogen addition, nutrient release

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18318 An Analysis of Relation Between Soil Radon Anomalies and Geological Environment Change

Authors: Mengdi Zhang, Xufeng Liu, Zhenji Gao, Ying Li, Zhu Rao, Yi Huang

Abstract:

As an open system, the earth is constantly undergoing the transformation and release of matter and energy. Fault zones are relatively discontinuous and fragile geological structures, and the release of material and energy inside the Earth is strongest in relatively weak fault zones. Earthquake events frequently occur in fault zones and are closely related to tectonic activity in these zones. In earthquake precursor observation, monitoring the spatiotemporal changes in the release of related gases near fault zones (such as radon gas, hydrogen, carbon dioxide, helium), and analyzing earthquake precursor anomalies, can be effective means to forecast the occurrence of earthquake events. Radon gas, as an inert radioactive gas generated during the decay of uranium and thorium, is not only a indicator for monitoring tectonic and seismic activity, but also an important topic for ecological and environmental health, playing a crucial role in uranium exploration. At present, research on soil radon gas mainly focuses on the measurement of soil gas concentration and flux in fault zone profiles, while research on the correlation between spatiotemporal concentration changes in the same region and its geological background is relatively little. In this paper, Tangshan area in north China is chosen as research area. An analysis was conducted on the seismic geological background of Tangshan area firstly. Then based on quantitative analysis and comparison of measurement radon concentrations of 2023 and 2010, combined with the study of seismic activity and environmental changes during the time period, the spatiotemporal distribution characteristics and influencing factors were explored, in order to analyze the gas emission characteristics of the Tangshan fault zone and its relationship with fault activity, which aimed to be useful for the future work in earthquake monitor of Tangshan area.

Keywords: radon, Northern China, soil gas, earthquake

Procedia PDF Downloads 39
18317 Modification of Titanium Surfaces with Micro/Nanospheres for Local Antibiotic Release

Authors: Burcu Doymus, Fatma N. Kok, Sakip Onder

Abstract:

Titanium and titanium-based materials are commonly used to replace or regenerate the injured or lost tissues because of accidents or illnesses. Hospital infections and strong bond formation at the implant-tissue interface are directly affecting the success of the implantation as weak bonding with the native tissue and hospital infections lead to revision surgery. The purpose of the presented study is to modify the surface of the titanium substrates with nano/microspheres for local drug delivery and to prevent hospital infections. Firstly, titanium surfaces were silanized with APTES (3-Triethoxysilylpropylamine) following the negatively charged oxide layer formation. Then characterization studies using Scanning Electron Microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) were done on the modified surfaces. Secondly, microspheres/nanospheres were prepared with chitosan that is a natural polymer and having valuable properties such as non-toxicity, high biocompatibility, low allergen city and biodegradability for biomedical applications. Antibiotic (ciprofloxacin) loaded micro/nanospheres have been fabricated using emulsion cross-linking method and have been immobilized onto the titanium surfaces with different immobilization techniques such as covalent bond and entrapment. Optimization studies on size and drug loading capacities of micro/nanospheres were conducted before the immobilization process. Light microscopy and SEM were used to visualize and measure the size of the produced micro/nanospheres. Loaded and released drug amounts were determined by using UV- spectrophotometer at 278 nm. Finally, SEM analysis and drug release studies on the micro/nanospheres coated Ti surfaces were done. As a conclusion, it was shown that micro/nanospheres were immobilized onto the surfaces successfully and drug release from these surfaces was in a controlled manner. Moreover, the density of the micro/nanospheres after the drug release studies was higher on the surfaces where the entrapment technique was used for immobilization. Acknowledgement: This work is financially supported by The Scientific and Technological Research Council Of Turkey (Project # 217M220)

Keywords: chitosan, controlled drug release, nanosphere, nosocomial infections, titanium

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18316 Therapeutic Potential of GSTM2-2 C-Terminal Domain and Its Mutants, F157A and Y160A on the Treatment of Cardiac Arrhythmias: Effect on Ca2+ Transients in Neonatal Ventricular Cardiomyocytes

Authors: R. P. Hewawasam, A. F. Dulhunty

Abstract:

The ryanodine receptor (RyR) is an intracellular ion channel that releases Ca2+ from the sarcoplasmic reticulum and is essential for the excitation-contraction coupling and contraction in striated muscle. Human muscle specific glutathione transferase M2-2 (GSTM2-2) is a highly specific inhibitor of cardiac ryanodine receptor (RyR2) activity. Single channel-lipid bilayer studies and Ca2+ release assays performed using the C-terminal half of the GSTM2-2 and its mutants F157A and Y160A confirmed the ability of the C terminal domain of GSTM2-2 to specifically inhibit the cardiac ryanodine receptor activity. Objective of the present study is to determine the effect of C terminal domain of GSTM2-2 (GSTM2-2C) and the mutants, F157A and Y160A on the Ca2+ transients of neonatal ventricular cardiomyocytes. Primary cardiomyocytes were cultured from neonatal rats. They were treated with GSTM2-2C and the two mutants F157A and Y160A at 15µM and incubated for 2 hours. Then the cells were led with Fluo-4AM, fluorescent Ca2+ indicator, and the field stimulated (1 Hz, 3V and 2ms) cells were excited using the 488 nm argon laser. Contractility of the cells were measured and the Ca2+ transients in the stained cells were imaged using Leica SP5 confocal microscope. Peak amplitude of the Ca2+ transient, rise time and decay time from the peak were measured for each transient. In contrast to GSTM2C which significantly reduced the % shortening (42.8%) in the field stimulated cells, F157A and Y160A failed to reduce the % shortening.Analysis revealed that the average amplitude of the Ca2+ transient was significantly reduced (P<0.001) in cells treated with the wild type GSTM2-2C compared to that of untreated cells. Cells treated with the mutants F157A and Y160A didn’t change the Ca2+ transient significantly compared to the control. A significant increase in the rise time (P< 0.001) and a significant reduction in the decay time (P< 0.001) were observed in cardiomyocytes treated with GSTM2-2C compared to the control but not with F157A and Y160A. These results are consistent with the observation that GSTM2-2C reduced the Ca2+ release from the cardiac SR significantly whereas the mutants, F157A and Y160A didn’t show any effect compared to the control. GSTM2-2C has an isoform-specific effect on the cardiac ryanodine receptor activity and also it inhibits RyR2 channel activity only during diastole. Selective inhibition of RyR2 by GSTM2-2C has significant clinical potential in the treatment of cardiac arrhythmias and heart failure. Since GSTM2-2C-terminal construct has no GST enzyme activity, its introduction to the cardiomyocyte would not exert any unwanted side effects that may alter its enzymatic action. The present study further confirms that GSTM2-2C is capable of decreasing the Ca2+ release from the cardiac SR during diastole. These results raise the future possibility of using GSTM2-2C as a template for therapeutics that can depress RyR2 function when the channel is hyperactive in cardiac arrhythmias and heart failure.

Keywords: arrhythmia, cardiac muscle, cardiac ryanodine receptor, GSTM2-2

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18315 Statistical Analysis of Interferon-γ for the Effectiveness of an Anti-Tuberculous Treatment

Authors: Shishen Xie, Yingda L. Xie

Abstract:

Tuberculosis (TB) is a potentially serious infectious disease that remains a health concern. The Interferon Gamma Release Assay (IGRA) is a blood test to find out if an individual is tuberculous positive or negative. This study applies statistical analysis to the clinical data of interferon-gamma levels of seventy-three subjects who diagnosed pulmonary TB in an anti-tuberculous treatment. Data analysis is performed to determine if there is a significant decline in interferon-gamma levels for the subjects during a period of six months, and to infer if the anti-tuberculous treatment is effective.

Keywords: data analysis, interferon gamma release assay, statistical methods, tuberculosis infection

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18314 Effect of Mechanical Loading on the Delamination of Stratified Composite in Mode I

Authors: H. Achache, Y. Madani, A. Benzerdjeb

Abstract:

The present study is based on the three-dimensional digital analysis by the finite elements method of the mechanical loading effect on the delamination of unidirectional and multidirectional stratified composites. The aim of this work is the determination of the release energy rate G in mode I and the Von Mises equivalent constraint distribution along the damaged area under the influence of several parameters such as the applied load and the delamination size. The results obtained in this study show that the unidirectional composite laminates have better mechanical resistance one the loading line than the multidirectional composite laminates.

Keywords: delamination, release energy rate, stratified composite, finite element method, ply

Procedia PDF Downloads 395
18313 pH and Thermo-Sensitive Nanogels for Anti-Cancer Therapy

Authors: V. Naga Sravan Kumar Varma, H. G. Shivakumar

Abstract:

The aim of the study was to develop dual sensitive poly (N-isopropylacrylamide-co-acrylic acid) (PNA) nanogels(NGs) and studying its applications for Anti-Cancer therapy. NGs were fabricated by free radical polymerization using different amount of N-isopropylacrylamide and acrylic acid. A study for polymer composition over the effect on LCST in different pH was evaluated by measuring the absorbance at 500nm using UV spectrophotometer. Further selected NG’s were evaluated for change in hydrodynamic diameters in response to pH and temperature. NGs which could sharply respond to low pH value of cancer cells at body temperature were loaded with Fluorouracil (5-FU) using equilibrium swelling method and studied for drug release behaviour in different pH. A significant influence of NGs polymer composition over pH dependent LCST was observed. NGs which were spherical with an average particle size of 268nm at room temperature, shrinked forming an irregular shape when heated above to their respective LCST. 5FU loaded NGs did not intervene any difference in pH depended LCST behaviour of NGs. The in vitro drug release of NGs exhibited a pH and thermo-dependent control release. The cytoxicity study of blank carrier to MCF7 cell line showed no cytotoxicity. The results indicated that PNA NGs could be used as a potential drug carrier for anti-cancer therapy.

Keywords: pH and thermo-sensitive, nanogels, P(NIPAM-co-AAc), anti-cancer, 5-FU

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18312 Optimizing Fire Suppression Time in Buildings by Forming a Fire Feedback Loop

Authors: Zhdanova A. O., Volkov R. S., Kuznetsov G. V., Strizhak P. A.

Abstract:

Fires in different types of facilities are a serious problem worldwide.It is still an unaccomplished science and technology objective to establish the minimum number and type of sensors in automatic systems of compartment fire suppression which would turn the fire-extinguishing agent spraying on and off in real time depending on the state of the fire, minimize the amount of agent applied, delay time in fire suppression and system response, as well as the time of combustion suppression. Based on the results of experimental studies, the conclusion was made that it is reasonable to use a gas analysis system and heat sensors (in the event of their prior activation) to determine the effectiveness of fire suppression (fire-extinguishing composition interacts with the fire). Thus, the concentration of CO in the interaction of the firefighting liquid with the fire increases to 0.7–1.2%, which indicates a slowdown in the flame combustion, and heat sensors stop responding at a gas medium temperature below 80 ºC, which shows a gradual decrease in the heat release from the fire. The evidence from this study suggests that the information received from the video recording equipment (video camera) should be used in real time as an additional parameter confirming fire suppression. Research was supported by Russian Science Foundation (project No 21-19-00009, https://rscf.ru/en/project/21-19-00009/).

Keywords: compartment fires, fire suppression, continuous control of fire behavior, feedback systems

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18311 Design and Characterization of Aromatase Inhibitor Loaded Nanoparticles for the Treatment of Breast Cancer

Authors: Harish K. Chandrawanshi, Mithun S. Rajput, Neelima Choure, Purnima Dey Sarkar, Shailesh Jain

Abstract:

The present research study aimed to fabricate and evaluate biodegradable nanoparticles of aromatase inhibitor letrozole, intended for breast cancer therapy. Letrozole loaded poly(D,L-lactide-co-glycolide acid) nanoparticles were prepared by solvent evaporation method using dichlorometane as solvent (oil phase) and polyvinyl alcohol (PVA) as aqueous phase. Prepared nanoparticles were characterized by particle size, infrared spectra, drug loading efficiency, drug entrapment efficiency and in vitro release and also evaluated for in vivo anticancer activity. The high speed homogenizer was used to produce stable nanoparticles of mean size range 198.35 ± 0.04 nm with high entrapment efficiency (69.86 ± 2.78%). Percentage of drug and homogenization speed significantly influenced the particle size, entrapment efficiency and release (p<0.05). The nanoparticles show significant in vivo anticancer activity against Ehrlich ascites carcinoma in mice. The significant system sustained the release of letrozole drug effectively and further investigation could exhibit its potential usefulness in breast cancer therapy.

Keywords: breast cancer/therapy, letrozole, nanoparticles, PLGA

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18310 Antibacterial Effect of Silver Diamine Fluoride Incorporated in Fissure Sealants

Authors: Nélio Veiga, Paula Ferreira, Tiago Correia, Maria J. Correia, Carlos Pereira, Odete Amaral, Ilídio J. Correia

Abstract:

Introduction: The application of fissure sealants is considered to be an important primary prevention method used in dental medicine. However, the formation of microleakage gaps between tooth enamel and the fissure sealant applied is one of the most common reasons of dental caries development in teeth with fissure sealants. The association between various dental biomaterials may limit the major disadvantages and limitations of biomaterials functioning in a complementary manner. The present study consists in the incorporation of a cariostatic agent – silver diamine fluoride (SDF) – in a resin-based fissure sealant followed by the study of release kinetics by spectrophotometry analysis of the association between both biomaterials and assessment of the inhibitory effect on the growth of the reference bacterial strain Streptococcus mutans (S. mutans) in an in vitro study. Materials and Methods: An experimental in vitro study was designed consisting in the entrapment of SDF (Cariestop® 12% and 30%) into a commercially available fissure sealant (Fissurit®), by photopolymerization and photocrosslinking. The same sealant, without SDF was used as a negative control. The effect of the sealants on the growth of S. mutans was determined by the presence of bacterial inhibitory halos in the cultures at the end of the incubation period. In order to confirm the absence of bacteria in the surface of the materials, Scanning Electron Microscopy (SEM) characterization was performed. Also, to analyze the release profile of SDF along time, spectrophotometry technique was applied. Results: The obtained results indicate that the association of SDF to a resin-based fissure sealant may be able to increase the inhibition of S. mutans growth. However, no SDF release was noticed during the in vitro release studies and no statistical significant difference was verified when comparing the inhibitory halo sizes obtained for test and control group.  Conclusions: In this study, the entrapment of SDF in the resin-based fissure sealant did not potentiate the antibacterial effect of the fissure sealant or avoid the immediate development of dental caries. The development of more laboratorial research and, afterwards, long-term clinical data are necessary in order to verify if this association between these biomaterials is effective and can be considered for being used in oral health management. Also, other methodologies for associating cariostatic agents and sealant should be addressed.

Keywords: biomaterial, fissure sealant, primary prevention, silver diamine fluoride

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18309 Bioactive Substances-Loaded Water-in-Oil/Oil-in-Water Emulsions for Dietary Supplementation in the Elderly

Authors: Agnieszka Markowska-Radomska, Ewa Dluska

Abstract:

Maintaining a bioactive substances dense diet is important for the elderly, especially to prevent diseases and to support healthy ageing. Adequate bioactive substances intake can reduce the risk of developing chronic diseases (e.g. cardiovascular, osteoporosis, neurodegenerative syndromes, diseases of the oral cavity, gastrointestinal (GI) disorders, diabetes, and cancer). This can be achieved by introducing a comprehensive supplementation of components necessary for the proper functioning of the ageing body. The paper proposes the multiple emulsions of the W1/O/W2 (water-in-oil-in-water) type as carriers for effective co-encapsulation and co-delivery of bioactive substances in supplementation of the elderly. Multiple emulsions are complex structured systems ("drops in drops"). The functional structure of the W1/O/W2 emulsion enables (i) incorporation of one or more bioactive components (lipophilic and hydrophilic); (ii) enhancement of stability and bioavailability of encapsulated substances; (iii) prevention of interactions between substances, as well as with the external environment, delivery to a specific location; and (iv) release in a controlled manner. The multiple emulsions were prepared by a one-step method in the Couette-Taylor flow (CTF) contactor in a continuous manner. In general, a two-step emulsification process is used to obtain multiple emulsions. The paper contains a proposal of emulsion functionalization by introducing pH-responsive biopolymer—carboxymethylcellulose sodium salt (CMC-Na) to the external phase, which made it possible to achieve a release of components controlled by the pH of the gastrointestinal environment. The membrane phase of emulsions was soybean oil. The W1/O/W2 emulsions were evaluated for their characteristics (drops size/drop size distribution, volume packing fraction), encapsulation efficiency and stability during storage (to 30 days) at 4ºC and 25ºC. Also, the in vitro multi-substance co-release process were investigated in a simulated gastrointestinal environment (different pH and composition of release medium). Three groups of stable multiple emulsions were obtained: emulsions I with co-encapsulated vitamins B12, B6 and resveratrol; emulsions II with vitamin A and β-carotene; and emulsions III with vitamins C, E and D3. The substances were encapsulated in the appropriate emulsion phases depending on the solubility. For all emulsions, high encapsulation efficience (over 95%) and high volume packing fraction of internal droplets (0.54-0.76) were reached. In addition, due to the presence of a polymer (CMC-Na) with adhesive properties, high encapsulation stability during emulsions storage were achieved. The co-release study of encapsulated bioactive substances confirmed the possibility to modify the release profiles. It was found that the releasing process can be controlled through the composition, structure, physicochemical parameters of emulsions and pH of the release medium. The results showed that the obtained multiple emulsions might be used as potential liquid complex carriers for controlled/modified/site-specific co-delivery of bioactive substances in dietary supplementation in the elderly.

Keywords: bioactive substance co-release, co-encapsulation, elderly supplementation, multiple emulsion

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18308 Formulation and Characterization of Antimicrobial Herbal Mouthwash from Some Herbal Extracts for Treatment of Periodontal Diseases

Authors: Reenu Yadav, Abhay Asthana, S. K. Yadav

Abstract:

Purpose: The aim of the present work was to develop an oral gel for brushing with an antimicrobial activity which will cure/protect from various periodontal diseases such as periodontitis, gingivitis, and pyorrhea. Methods: Plant materials procured from local suppliers, extracted and standardized. Screening of antimicrobial activity was carried out with the help of disk diffusion method. The gel was formulated by dried extracts of Beautea monosperma and Cordia obliquus. Gels were evaluated on various parameters and standardization of the formulation was performed. The release of drugs was studied in pH 6.8 using a mastication device.Total phenolic and flavonoid contents were estimated by folin-Ciocalteu and aluminium chloride method, and stability studies were performed (40°C and RH 75% ± 5% for 90 days) to assess the effect of temperature and humidity on the concentration of phenolic and flavonoid contents. The results of accelerated stability conditions were compared with that of samples kept at controlled conditions (RT). The control samples were kept at room temperature (25°C, 35% RH for 180 days). Results: Results are encouraging; extracts possess significant antimicrobial activity at very low concentration (15µg/disc, 20µg/disc and 15 µg/ disc) on oral pathogenic bacteria. The formulation has optimal characteristics, as well as has a pleasant appearance, fragrance, texture, and taste, is highly acceptable by the volunteers. The diffusion coefficient values ranged from 0.6655 to 0.9164. Since the R values of korsmayer papas were close to 1, Drug release from formulation follows matrix diffusion kinetics. Hence, diffusion was the mechanism of the drug release. Formulation follows non-Fickian transport mechanism. Most Formulations released 50 % of their contents within 25-30 minutes. Results obtained from the accelerated stability studies are indicative of a slight reduction in flavonoids and phenolic contents with time on long time storage. When measured degradation under ambient conditions, degradation was significantly lower than in accelerated stability study. Conclusion: Plant extracts possess compounds with antimicrobial properties can be used as. Developed formulation will cure/protect from various periodontal diseases. Further development and evaluations oral gel including the isolated compounds on the commercial scale and their clinical and toxicological studies are the future challenges.

Keywords: herbal gel, dental care, ambient conditions, commercial scale

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18307 Preparation and Evaluation of siRNA Loaded Polymeric Nanoparticles

Authors: Riddhi Trivedi, Shrenik Shah

Abstract:

For Si RNA to be delivered various biodegradable polymers are trialed by many researchers. One of them is Chitosan (CS) nanoparticles which have been extensively studied for siRNA delivery but the stability and efficacy of such particles are highly dependent on the types of cross-linker used. Hence the attempts are made in this study with PGA To address this issue, three common cross-linkers; Ethylene glycol diacrylate (ED) and poly-D-glutamic acid (PGA) were used to prepare siRNA loaded CS-ED/PGA nanoparticles by ionic gelation method. The nanoparticles which were obtained were compared for its characterization in terms of its physicochemical properties i.e. particle size of the resultant particles, zeta potential, its encapsulation capacity in the polymer. Among all the formulations prepared with different crosslinker PGA siRNA had the smallest particle size (ranged from 120 ± 1.7 to 500 ± 10.9 nm) with zeta potential ranged from 22.1 ± 1.5 to +32.4 ± 0.5 mV, and high entrapment ( > 91%) and binding efficiencies. Similarly, CS-ED nanoparticles showed better siRNA protection during storage at 4˚C and as determined by serum protection assay. TEM micrographs revealed the assorted morphology of CS-PGA-siRNA nanoparticles in contrast to irregular morphology displayed by CS-ED-siRNA. All siRNA loaded nanoparticles were found to give initial burst release which after some time followed by a sustained release of siRNA which were loaded inside. All the formulations showed concentration-dependent cytotoxicity with when cytotoxicity performed by HeLa and normal vero cell lines.

Keywords: chitosan, siRNA, cytotoxicity, cell line study

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18306 Transdermal Medicated- Layered Extended-Release Patches for Co-delivery of Carbamazepine and Pyridoxine

Authors: Sarah K. Amer, Walaa Alaa

Abstract:

Epilepsy is an important cause of mortality and morbidity, according to WHO statistics. It is characterized by the presence of frequent seizures occurring more than 24 hours apart. Carbamazepine (CBZ) is considered first-line treatment for epilepsy. However, reports have shown that CBZ oral formulations failed to achieve optimum systemic delivery, minimize side effects, and enhance patient compliance. Besides, the literature has signified the lack of therapeutically efficient CBZ transdermal formulation and the urge for its existence owing to its ease and convenient method of application and highlighted capability to attain higher bioavailability and more extended-release profiles compared to conventional oral CBZ tablets. This work aims to prepare CBZ microspheres (MS) that are embedded in a transdermal gel containing Vitamin B to be co-delivered. MS were prepared by emulsion-solvent diffusion method using Eudragit S as core forming polymer and hydroxypropyl methylcellulose (HPMC) polymer. The MS appeared to be spherical and porous in nature, offering a large surface area and high entrapment efficiency of CBZ. The transdermal gel was prepared by solvent-evaporation technique using HPMC that, offered high entrapment efficiency and Eudragit S that provided an extended-release profile. Polyethylene glycol, Span 80 and Pyridoxine were also added. Data indicated that combinations of CBZ with pyridoxine can reduce epileptic seizures without affecting motor coordination. Extended-release profiles were evident for this system. The patches were furthermore tested for thickness, moisture content, folding endurance, spreadability and viscosity measurements. This novel pharmaceutical formulation would be of great influence on seizure control, offering better therapeutic effects.

Keywords: epilepsy, carbamazepine, pyridoxine, transdermal

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18305 Lipid Nanoparticles for Spironolactone Delivery: Physicochemical Characteristics, Stability and Invitro Release

Authors: H. R. Kelidari, M. Saeedi, J. Akbari, K. Morteza-Semnani, H. Valizadeh

Abstract:

Spironolactoe (SP) a synthetic steroid diuretic is a poorly water-soluble drug with a low and variable oral bioavailability. Regarding to the good solubility of SP in lipid materials, SP loaded Solid lipid nanoparticles (SP-SLNs) and nanostructured lipid carrier (SP-SLNs) were thus prepared in this work for accelerating dissolution of this drug. The SP loaded NLC with stearic acid (SA) as solid lipid and different Oleic Acid (OA) as liquid lipid content and SLN without OA were prepared by probe ultrasonication method. With increasing the percentage of OA from 0 to 30 wt% in SLN/NLC, the average size and zeta potential of nanoparticles felled down and entrapment efficiency (EE %) rose dramatically. The obtained micrograph particles showed pronounced spherical shape. Differential Scanning Calorimeter (DSC) measurements indicated that the presence of OA reduced the melting temperature and melting enthalpy of solid lipid in NLC structure. The results reflected good long-term stability of the nanoparticles and the measurements show that the particle size remains lower in NLC compare to SLN formulations, 6 months after production. Dissolution of SP-SLN and SP-NLC was about 5.1 and 7.2 times faster than raw drugs in 120 min respectively. These results indicated that the SP loaded NLC containing 70:30 solid lipid to liquid lipid ratio is a suitable carrier of SP with improved drug EE and steady drug release properties.

Keywords: drug release, lipid nanoparticles, spironolactone, stability

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18304 Reforms in China's Vaccine Administration: Vulnerabilities, Legislative Progresses and the Systemic View of Vaccine Administration Law

Authors: Lin Tang, Xiaoxia Guo, Lingling Zhang

Abstract:

Recent vaccine scandals overshadowed China’s accomplishment of public health, triggering discussions on the causes of vaccine incidents. Through legal interpretation of selected vaccine incidents and analysis of systemic vulnerabilities in vaccine circulation and lot release, a panoramic review of legislative progresses in the vaccine administration sheds the light on this debate. In essence, it is the combination of the lagging legal system and the absence of information technology infrastructure in the process of vaccine administration reform that has led to the recurrence of vaccine incidents. These findings have significant implications for further improvement of vaccine administration and China’s participation in global healthcare.

Keywords: legislation, lot release, public health, reform, vaccine administration, vaccine circulation

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18303 Bioresorbable Medicament-Eluting Grommet Tube for Otitis Media with Effusion

Authors: Chee Wee Gan, Anthony Herr Cheun Ng, Yee Shan Wong, Subbu Venkatraman, Lynne Hsueh Yee Lim

Abstract:

Otitis media with effusion (OME) is the leading cause of hearing loss in children worldwide. Surgery to insert grommet tube into the eardrum is usually indicated for OME unresponsive to antimicrobial therapy. It is the most common surgery for children. However, current commercially available grommet tubes are non-bioresorbable, not drug-treated, with unpredictable duration of retention on the eardrum to ventilate middle ear. Their functionality is impaired when clogged or chronically infected, requiring additional surgery to remove/reinsert grommet tubes. We envisaged that a novel fully bioresorbable grommet tube with sustained antibiotic release technology could address these drawbacks. In this study, drug-loaded bioresorbable poly(L-lactide-co-ε-caprolactone)(PLC) copolymer grommet tubes were fabricated by microinjection moulding technique. In vitro drug release and degradation model of PLC tubes were studied. Antibacterial property was evaluated by incubating PLC tubes with P. aeruginosa broth. Surface morphology was analyzed using scanning electron microscopy. A preliminary animal study was conducted using guinea pigs as an in vivo model to evaluate PLC tubes with and without drug, with commercial Mini Shah grommet tube as comparison. Our in vitro data showed sustained drug release over 3 months. All PLC tubes revealed exponential degradation profiles over time. Modeling predicted loss of tube functionality in water to be approximately 14 weeks and 17 weeks for PLC with and without drug, respectively. Generally, PLC tubes had less bacteria adherence, which were attributed to the much smoother tube surfaces compared to Mini Shah. Antibiotic from PLC tube further made bacteria adherence on surface negligible. They showed neither inflammation nor otorrhea after 18 weeks post-insertion in the eardrums of guinea pigs, but had demonstrated severe degree of bioresorption. Histology confirmed the new PLC tubes were biocompatible. Analyses on the PLC tubes in the eardrums showed bioresorption profiles close to our in vitro degradation models. The bioresorbable antibiotic-loaded grommet tubes showed good predictability in functionality. The smooth surface and sustained release technology reduced the risk of tube infection. Tube functional duration of 18 weeks allowed sufficient ventilation period to treat OME. Our ongoing studies include modifying the surface properties with protein coating, optimizing the drug dosage in the tubes to enhance their performances, evaluating their functional outcome on hearing after full resoption of grommet tube and healing of eardrums, and developing animal model with OME to further validate our in vitro models.

Keywords: bioresorbable polymer, drug release, grommet tube, guinea pigs, otitis media with effusion

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18302 Preparation of Biomedical Hydrogels Using Phenolic Compounds and Electron Beam Irradiation

Authors: Farnaz Sadeghi, Moslem Tavakol

Abstract:

In this study, an attempt has been made to prepare a physically cross-linked gel by cooling of tannic acid (TA)-polyvinyl alcohol (PVA) solution that subsequently convert to antibacterial chemically cross-linked hydrogel by using electron beam irradiation. PVA is known for its biocompatibility and hydrophilicity, and TA is known for being a natural compound which can serve as a cross-linking agent and a therapeutic agent. Swelling behavior, gel content, pore size, and mechanical properties of hydrogels which prepared at 14, 28, and 56 (kGy) with different ratios of polymers were investigated. PVA-TA hydrogel showed sustained release of tannic acid as approximately 20% and 50% of loaded TA released from the hydrogel after 4 and 72 h release time. We found that gel content decreased and the moisture retention capability increased by an increase in TA composition. In addition, PVA-TA hydrogels showed a good antibacterial activity against S.aureus. MTT analysis indicated that close to 83% of fibroblast cells remained viable after 48 h exposure to hydrogel extract. Moreover, the cooling of 10% PVA solution containing 0.5 and 0.75% w/v tannic acid to room and refrigerator, respectively, led to formation of physical gel that did not present any flow index after inversion of hydrogel cast. According to the results, the hydrogel prepared by electron beam irradiation of blended PVA-TA solution could be further investigated as a promising candidate for wound healing.

Keywords: poly vinyl alcohol, tannic acid, electron beam irradiation, hydrogel wound dressing

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18301 Numerical Simulation of Production of Microspheres from Polymer Emulsion in Microfluidic Device toward Using in Drug Delivery Systems

Authors: Nizar Jawad Hadi, Sajad Abd Alabbas

Abstract:

Because of their ability to encapsulate and release drugs in a controlled manner, microspheres fabricated from polymer emulsions using microfluidic devices have shown promise for drug delivery applications. In this study, the effects of velocity, density, viscosity, and surface tension, as well as channel diameter, on microsphere generation were investigated using Fluent Ansys software. The software was programmed with the physical properties of the polymer emulsion such as density, viscosity and surface tension. Simulation will then be performed to predict fluid flow and microsphere production and improve the design of drug delivery applications based on changes in these parameters. The effects of capillary and Weber numbers are also studied. The results of the study showed that the size of the microspheres can be controlled by adjusting the speed and diameter of the channel. Narrower microspheres resulted from narrower channel widths and higher flow rates, which could improve drug delivery efficiency, while smaller microspheres resulted from lower interfacial surface tension. The viscosity and density of the polymer emulsion significantly affected the size of the microspheres, ith higher viscosities and densities producing smaller microspheres. The loading and drug release properties of the microspheres created with the microfluidic technique were also predicted. The results showed that the microspheres can efficiently encapsulate drugs and release them in a controlled manner over a period of time. This is due to the high surface area to volume ratio of the microspheres, which allows for efficient drug diffusion. The ability to tune the manufacturing process using factors such as speed, density, viscosity, channel diameter, and surface tension offers a potential opportunity to design drug delivery systems with greater efficiency and fewer side effects.

Keywords: polymer emulsion, microspheres, numerical simulation, microfluidic device

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18300 Formulation and Evaluation of Lisinopril Microspheres for Nasal Delivery

Authors: S. S. Patil, R. M. Mhetre, S. V. Patil

Abstract:

Lisinopril is an angiotensin converting enzyme inhibitor used in the treatment of hypertension and heart failure in prophylactic treatment after myocardial infarction and in diabetic nephropathy. However, it is very poorly absorbed from gastro-intestinal tract. Intranasal administration is an ideal alternative to the parenteral route for systemic drug delivery. Formulating multiparticulate system with mucoadhesive polymers provide a significant increase in the nasal residence time. The aim of the present approach was to overcome the drawbacks of the conventional dosage forms of lisinopril by formulating intranasal microspheres with Carbopol 974P NF and HPMC K4 M along with film forming polymer ethyl cellulose.The microspheres were prepared by emulsion solvent evaporation method. The prepared microspheres were characterized for encapsulation efficiency, drug loading, particle size, and surface morphology, degree of swelling, ex vivo mucoadhesion, drug release, ex vivo diffusion studies. All formulations has shown entrapment efficiency between 80 to more than 95%, mucoadhesion was more than 80 % and drug release up to 90 %. Ex vivo studies revealed tht the improved bioavailability of drug compared to oral drug administration. Both in vitro and in vivo studies conclude that combination of Carbopol and HPMC based microspheres shown better results than single carbopol based microspheres for the delivery of lisinopril.

Keywords: microspheres, lisinopril, nasal delivery, solvent evaporation method

Procedia PDF Downloads 502
18299 Microfiber Release During Laundry Under Different Rinsing Parameters

Authors: Fulya Asena Uluç, Ehsan Tuzcuoğlu, Songül Bayraktar, Burak Koca, Alper Gürarslan

Abstract:

Microplastics are contaminants that are widely distributed in the environment with a detrimental ecological effect. Besides this, recent research has proved the existence of microplastics in human blood and organs. Microplastics in the environment can be divided into two main categories: primary and secondary microplastics. Primary microplastics are plastics that are released into the environment as microscopic particles. On the other hand, secondary microplastics are the smaller particles that are shed as a result of the consumption of synthetic materials in textile products as well as other products. Textiles are the main source of microplastic contamination in aquatic ecosystems. Laundry of synthetic textiles (34.8%) accounts for an average annual discharge of 3.2 million tons of primary microplastics into the environment. Recently, microfiber shedding from laundry research has gained traction. However, no comprehensive study was conducted from the standpoint of rinsing parameters during laundry to analyze microfiber shedding. The purpose of the present study is to quantify microfiber shedding from fabric under different rinsing conditions and determine the effective rinsing parameters on microfiber release in a laundry environment. In this regard, a parametric study is carried out to investigate the key factors affecting the microfiber release from a front-load washing machine. These parameters are the amount of water used during the rinsing step and the spinning speed at the end of the washing cycle. Minitab statistical program is used to create a design of the experiment (DOE) and analyze the experimental results. Tests are repeated twice and besides the controlled parameters, other washing parameters are kept constant in the washing algorithm. At the end of each cycle, released microfibers are collected via a custom-made filtration system and weighted with precision balance. The results showed that by increasing the water amount during the rinsing step, the amount of microplastic released from the washing machine increased drastically. Also, the parametric study revealed that increasing the spinning speed results in an increase in the microfiber release from textiles.

Keywords: front load, laundry, microfiber, microfiber release, microfiber shedding, microplastic, pollution, rinsing parameters, sustainability, washing parameters, washing machine

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18298 Influence of Valve Lift Timing on Producer Gas Combustion and Its Modeling Using Two-Stage Wiebe Function

Authors: M. Sreedhar Babu, Vishal Garg, S. B. Akella, Shibu Clement, N. K. S Rajan

Abstract:

Producer gas is a biomass derived gaseous fuel which is extensively used in internal combustion engines for power generation application. Unlike the conventional hydrocarbon fuels (Gasoline and Natural gas), the combustion properties of producer gas fuel are much different. Therefore, setting of optimal spark time for efficient engine operation is required. Owing to the fluctuating tendency of producer gas composition during gasification process, the heat release patterns (dictating the power output and emissions) obtained are quite different from conventional fuels. It was found that, valve lift timing is yet another factor which influences the burn rate of producer gas fuel, and thus, the heat release rate of the engine. Therefore, the present study was motivated to estimate the influence of valve lift timing analytically (Wiebe model) on the burn rate of producer gas through curve fitting against experimentally obtained mass fraction burn curves of several producer gas compositions. Furthermore, Wiebe models are widely used in zero-dimensional codes for engine parametric studies and are quite popular. This study also addresses the influence of hydrogen and methane concentration of producer gas on combustion trends, which are known to cause dynamics in engine combustion.

Keywords: combustion duration (CD), crank angle (CA), mass fraction burnt (MFB), producer sas (PG), Wiebe Combustion Model (WCM), wide open throttle (WOT)

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18297 Management and Evaluation of the Importance of Porous Media in Biomedical Engineering as Associated with Magnetic Resonance Imaging Besides Drug Delivery

Authors: Fateme Nokhodchi Bonab

Abstract:

Studies related to magnetic resonance imaging (MRI) and drug delivery are reviewed in this study to demonstrate the role of transport theory in porous media in facilitating advances in biomedical applications. Diffusion processes are believed to be important in many therapeutic modalities such as: B. Delivery of drugs to the brain. We analyse the progress in the development of diffusion equations using the local volume average method and the evaluation of applications related to diffusion equations. Torsion and porosity have significant effects on diffusive transport. In this study, various relevant models of torsion are presented and mathematical modeling of drug release from biodegradable delivery systems is analysed. In this study, a new model of drug release kinetics from porous biodegradable polymeric microspheres under bulk and surface erosion of the polymer matrix is presented. Solute drug diffusion, drug dissolution from the solid phase, and polymer matrix erosion have been found to play a central role in controlling the overall drug release process. This work paves the way for MRI and drug delivery researchers to develop comprehensive models based on porous media theory that use fewer assumptions compared to other approaches.

Keywords: MRI, porous media, drug delivery, biomedical applications

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18296 Development and in vitro Characterization of Loteprednol Etabonate-Loaded Polymeric Nanoparticles for Ocular Delivery

Authors: Abhishek Kumar Sah, Preeti K. Suresh

Abstract:

Effective drug delivery to the eye is a massive challenge, due to complicated physiological ocular barriers, rapid washout by tear and nasolachrymal drainage. Thus, most of the conventional ophthalmic formulations face the problem of low ocular bioavailability. Ophthalmic drug therapy can be improved by enhancing the precorneal drug retention along with improved drug penetration. The aim of the present investigation was to develop and evaluate a biodegradable polymer poly (D, L-lactide-co-glycolide) (PLGA) coated nanoparticulate carrier of loteprednol etabonate. PLGA nanoparticles were prepared by modified emulsification/solvent diffusion method using high-speed homogenizer followed by sonication. The nanoparticles were characterized for various parameters such as particle size, zeta potential, polydispersity index, X-ray powder diffraction (XRD), Transmission electron microscopy (TEM), in vitro drug release profile and stability. The prepared nanocarriers displayed mean particle size in the range of 271.7 to 424.4 nm, with zeta potential less than –10 mV. In vitro release in simulated tear fluid (STF) nanocarrier showed an extended release profile of loteprednol etabonate. TEM confirmed the spherical morphology and smooth surface of the particles. All the prepared formulations were found to be stable at varying temperatures.

Keywords: drug delivery, ocular delivery, polymeric nanoparticles, loteprednol etabonate

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18295 Overall Function and Symptom Impact of Self-Applied Myofascial Release in Adult Patients With Fibromyalgia. A Seven-Week Pilot Study

Authors: Domenica Tambasco, Riina Bray, Sophia Jaworski, Gillian Grant, Celeste Corkery

Abstract:

Fibromyalgia is a chronic condition characterized by widespread musculoskeletal pain, fatigue, and reduced function. Management of symptoms include medications, physical treatments and mindfulness therapies. Myofascial Release is a modality that has been successfully applied in var-ious musculoskeletal conditions. However, to the author’s best knowledge, it is not yet recog-nized as a self-management therapy option in Fibromyalgia. In this study, we investigated whether Self-applied Myofascial Release (SMR) is associated with overall improved function and symptoms in Fibromyalgia. Methods: Eligible adult patients with a confirmed diagnosis of Fibromyalgia at Women’s College Hospital were recruited to SMR. Sessions ran for 1 hour once a week for 7 weeks, led by the same two Physiotherapists knowledgeable in this physical treat-ment modality. The main outcome measure was an overall impact score for function and symp-toms based on the validated assessment tool for Fibromyalgia, the Revised Fibromyalgia Impact Questionnaire (FIQR), measured pre and post-intervention. Both descriptive and analytical methods were applied and reported. Results: We analyzed results using a paired t-test to deter-mine if there was a statistically significant difference in mean FIQR scores between initial (pre-intervention) and final (post-intervention) scores. A clinically significant difference in FIQR was defined as a reduction in score by 10 or more points. Conclusions: Our pilot study showed that SMR appeared to be a safe and effective intervention for our Fibromyalgia participants and the overall impact on function and symptoms occurred in only 7 weeks. Further studies with larger sample sizes comparing SMR to other physical treatment modalities (such as stretching) in an RCT are recommended.

Keywords: fibromyalgia, myofascial release, physical therapy, FIQR

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18294 Polymeric Micelles Based on Block Copolymer α-Tocopherol Succinate-g-Carboxymethyl Chitosan for Tamoxifen Delivery

Authors: Sunil K. Jena, Sanjaya K. Samal, Mahesh Chand, Abhay T. Sangamwar

Abstract:

Tamoxifen (TMX) and its analogues are approved as a first line therapy for the treatment of estrogen receptor-positive tumors. However, clinical development of TMX has been hampered by its low bioavailability and severe hepatotoxicity. Herein, we attempt to design a new drug delivery vehicle that could enhance the pharmacokinetic performance of TMX. Initially, high-molecular weight carboxymethyl chitosan was hydrolyzed to low-molecular weight carboxymethyl chitosan (LMW CMC) with hydrogen peroxide under the catalysis of phosphotungstic acid. Amphiphilic block copolymers of LMW CMC were synthesized via amidation reaction between the carboxyl group of α-tocopherol succinate (TS) and an amine group of LMW CMC. These amphiphilic block copolymers were self-assembled to nanosize core-shell-structural micelles in the aqueous medium. The critical micelle concentration (CMC) decreased with the increasing substitution of TS on LMW CMC, which ranged from 1.58 × 10-6 to 7.94 × 10-8 g/mL. Maximum TMX loading up to 8.08 ± 0.98% was achieved with Cmc-TS4.5 (TMX/Cmc-TS4.5 with 1:8 weight ratio). Both blank and TMX-loaded polymeric micelles (TMX-PM) of Cmc-TS4.5 exhibits spherical shape with the particle size below 200 nm. TMX-PM has been found to be stable in the gastrointestinal conditions and released only 44.5% of the total drug content by the first 72 h in simulated gastric fluid (SGF), pH 1.2. However, the presence of pepsin does not significantly increased the TMX release in SGF, pH 1.2, released only about 46.2% by the first 72 h suggesting its inability to cleave the peptide bond. In contrast, the release of TMX from TMX-PM4.5 in SIF, pH 6.8 (without pancreatin) was slow and sustained, released only about 10.43% of the total drug content within the first 30 min and nearly about 12.41% by the first 72 h. The presence of pancreatin in SIF, pH 6.8 led to an improvement in drug release. About 28.09% of incorporated TMX was released in the presence of pancreatin in 72 h. A cytotoxicity study demonstrated that TMX-PM exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells. Pharmacokinetic studies on Sprague-Dawley rats revealed a remarkable increase in oral bioavailability (1.87-fold) with significant (p < 0.0001) enhancement in AUC0-72 h, t1/2 and MRT of TMX-PM4.5 than that of TMX-suspension. Thus, the results suggested that CMC-TS micelles are a promising carrier for TMX delivery.

Keywords: carboxymethyl chitosan, d-α-tocopherol succinate, pharmacokinetic, polymeric micelles, tamoxifen

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18293 Determination of the Toxicity of a Lunar Dust Simulant on Human Alveolar Epithelial Cells and Macrophages in vitro

Authors: Agatha Bebbington, Terry Tetley, Kathryn Hadler

Abstract:

Background: Astronauts will set foot on the Moon later this decade, and are at high risk of lunar dust inhalation. Freshly-fractured lunar dust produces reactive oxygen species in solution, which are known to cause cellular damage and inflammation. Cytotoxicity and inflammatory mediator release was measured in pulmonary alveolar epithelial cells (cells that line the gas-exchange zone of the lung) exposed to a lunar dust simulant, LMS-1. It was hypothesised that freshly-fractured LMS-1 would result in increased cytotoxicity and inflammatory mediator release, owing to the angular morphology and high reactivity of fractured particles. Methods: A human alveolar epithelial type 1-like cell line (TT1) and a human macrophage-like cell line (THP-1) were exposed to 0-200μg/ml of unground, aged-ground, and freshly-ground LMS-1 (screened at <22μm). Cell viability, cytotoxicity, and inflammatory mediator release (IL-6, IL-8) were assessed using MMT, LDH, and ELISA assays, respectively. LMS-1 particles were characterised for their size, surface area, and morphology before and after grinding. Results: Exposure to LMS-1 particles did not result in overt cytotoxicity in either TT1 epithelial cells or THP-1 macrophage-like cells. A dose-dependent increase in IL-8 release was observed in TT1 cells, whereas THP-1 cell exposure, even at low particle concentrations, resulted in increased IL-8 release. Both cytotoxic and pro-inflammatory responses were most marked and significantly greater in TT1 and THP-1 cells exposed to freshly-fractured LMS-1. Discussion: LMS-1 is a novel lunar dust simulant; this is the first study to determine its toxicological effects on respiratory cells in vitro. An increased inflammatory response in TT1 and THP-1 cells exposed to ground LMS-1 suggests that low particle size, increased surface area, and angularity likely contribute to toxicity. Conclusions: Evenlow levels of exposure to LMS-1 could result in alveolar inflammation. This may have pathological consequences for astronauts exposed to lunar dust on future long-duration missions. Future research should test the effect of low-dose, intermittent lunar dust exposure on the respiratory system.

Keywords: lunar dust, LMS-1, lunar dust simulant, long-duration space travel, lunar dust toxicity

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18292 Targeted Delivery of Sustained Release Polymeric Nanoparticles for Cancer Therapy

Authors: Jamboor K. Vishwanatha

Abstract:

Among the potent anti-cancer agents, curcumin has been found to be very efficacious against various cancer cells. Despite multiple medicinal benefits of curcumin, poor water solubility, poor physiochemical properties and low bioavailability continue to pose major challenges in developing a formulation for clinical efficacy. To improve its potential application in the clinical area, we formulated poly lactic-co-glycolic acid (PLGA) nanoparticles. The PLGA nanoparticles were formulated using solid-oil/water emulsion solvent evaporation method and then characterized for percent yield, encapsulation efficiency, surface morphology, particle size, drug distribution within nanoparticles and drug polymer interaction. Our studies showed the successful formation of smooth and spherical curcumin loaded PLGA nanoparticles with a high percent yield of about 92.01±0.13% and an encapsulation efficiency of 90.88±0.14%. The mean particle size of the nanoparticles was found to be 145nm. The in vitro drug release profile showed 55-60% drug release from the nanoparticles over a period of 24 hours with continued sustained release over a period of 8 days. Exposure to curcumin loaded nanoparticles resulted in reduced cell viability of cancer cells compared to normal cells. We used a novel non-covalent insertion of a homo-bifunctional spacer for targeted delivery of curcumin to various cancer cells. Functionalized nanoparticles for antibody/targeting agent conjugation was prepared using a cross-linking ligand, bis(sulfosuccinimidyl) suberate (BS3), which has reactive carboxyl group to conjugate efficiently to the primary amino groups of the targeting agents. In our studies, we demonstrated successful conjugation of antibodies, Annexin A2 or prostate specific membrane antigen (PSMA), to curcumin loaded PLGA nanoparticles for targeting to prostate and breast cancer cells. The percent antibody attachment to PLGA nanoparticles was found to be 92.8%. Efficient intra-cellular uptake of the targeted nanoparticles was observed in the cancer cells. These results have emphasized the potential of our multifunctional curcumin nanoparticles to improve the clinical efficacy of curcumin therapy in patients with cancer.

Keywords: polymeric nanoparticles, cancer therapy, sustained release, curcumin

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18291 Characterization of Herberine Hydrochloride Nanoparticles

Authors: Bao-Fang Wen, Meng-Na Dai, Gao-Pei Zhu, Chen-Xi Zhang, Jing Sun, Xun-Bao Yin, Yu-Han Zhao, Hong-Wei Sun, Wei-Fen Zhang

Abstract:

A drug-loaded nanoparticles containing berberine hydrochloride (BH/FA-CTS-NPs) was prepared. The physicochemical characterizations of BH/FA-CTS-NPs and the inhibitory effect on the HeLa cells were investigated. Folic acid-conjugated chitosan (FA-CTS) was prepared by amino reaction of folic acid active ester and chitosan molecules; BH/FA-CTS-NPs were prepared using ionic cross-linking technique with BH as a model drug. The morphology and particle size were determined by Transmission Electron Microscope (TEM). The average diameters and polydispersity index (PDI) were evaluated by Dynamic Light Scattering (DLS). The interaction between various components and the nanocomplex were characterized by Fourier Transform Infrared Spectroscopy (FT-IR). The entrapment efficiency (EE), drug-loading (DL) and in vitro release were studied by UV spectrophotometer. The effect of cell anti-migratory and anti-invasive actions of BH/FA-CTS-NPs were investigated using MTT assays, wound healing assays, Annexin-V-FITC single staining assays, and flow cytometry, respectively. HeLa nude mice subcutaneously transplanted tumor model was established and treated with different drugs to observe the effect of BH/FA-CTS-NPs in vivo on HeLa bearing tumor. The BH/FA-CTS-NPs prepared in this experiment have a regular shape, uniform particle size, and no aggregation phenomenon. The results of DLS showed that mean particle size, PDI and Zeta potential of BH/FA-CTS NPs were (249.2 ± 3.6) nm, 0.129 ± 0.09, 33.6 ± 2.09, respectively, and the average diameter and PDI were stable in 90 days. The results of FT-IR demonstrated that the characteristic peaks of FA-CTS and BH/FA-CTS-NPs confirmed that FA-CTS cross-linked successfully and BH was encapsulated in NPs. The EE and DL amount were (79.3 ± 3.12) % and (7.24 ± 1.41) %, respectively. The results of in vitro release study indicated that the cumulative release of BH/FA-CTS NPs was (89.48±2.81) % in phosphate-buffered saline (PBS, pH 7.4) within 48h; these results by MTT assays and wund healing assays indicated that BH/FA-CTS NPs not only inhibited the proliferation of HeLa cells in a concentration and time-dependent manner but can induce apoptosis as well. The subcutaneous xenograft tumor formation rate of human cervical cancer cell line HeLa in nude mice was 98% after inoculation for 2 weeks. Compared with BH group and BH/CTS-NPs group, the xenograft tumor growth of BH/FA-CTS-NPs group was obviously slower; the result indicated that BH/FA-CTS-NPs could significantly inhibit the growth of HeLa xenograft tumor. BH/FA-CTS NPs with the sustained release effect could be prepared successfully by the ionic crosslinking method. Considering these properties, block proliferation and impairing the migration of the HeLa cell line, BH/FA-CTS NPs could be an important compound for consideration in the treatment of cervical cancer.

Keywords: folic-acid, chitosan, berberine hydrochloride, nanoparticles, cervical cancer

Procedia PDF Downloads 94