Search results for: oocyte release
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1244

Search results for: oocyte release

1034 Characteristics of Bio-hybrid Hydrogel Materials with Prolonged Release of the Model Active Substance as Potential Wound Dressings

Authors: Katarzyna Bialik-Wąs, Klaudia Pluta, Dagmara Malina, Małgorzata Miastkowska

Abstract:

In recent years, biocompatible hydrogels have been used more and more in medical applications, especially as modern dressings and drug delivery systems. The main goal of this research was the characteristics of bio-hybrid hydrogel materials incorporated with the nanocarrier-drug system, which enable the release in a gradual and prolonged manner, up to 7 days. Therefore, the use of such a combination will provide protection against mechanical damage and adequate hydration. The proposed bio-hybrid hydrogels are characterized by: transparency, biocompatibility, good mechanical strength, and the dual release system, which allows for gradual delivery of the active substance, even up to 7 days. Bio-hybrid hydrogels based on sodium alginate (SA), poly(vinyl alcohol) (PVA), glycerine, and Aloe vera solution (AV) were obtained through the chemical crosslinking method using poly(ethylene glycol) diacrylate as a crosslinking agent. Additionally, a nanocarrier-drug system was incorporated into SA/PVA/AV hydrogel matrix. Here, studies were focused on the release profiles of active substances from bio-hybrid hydrogels using the USP4 method (DZF II Flow-Through System, Erweka GmbH, Langen, Germany). The equipment incorporated seven in-line flow-through diffusion cells. The membrane was placed over support with an orifice of 1,5 cm in diameter (diffusional area, 1.766 cm²). All the cells were placed in a cell warmer connected with the Erweka heater DH 2000i and the Erweka piston pump HKP 720. The piston pump transports the receptor fluid via seven channels to the flow-through cells and automatically adapts the setting of the flow rate. All volumes were measured by gravimetric methods by filling the chambers with Milli-Q water and assuming a density of 1 g/ml. All the determinations were made in triplicate for each cell. The release study of the model active substance was carried out using a regenerated cellulose membrane Spectra/Por®Dialysis Membrane MWCO 6-8,000 Carl Roth® Company. These tests were conducted in buffer solutions – PBS at pH 7.4. A flow rate of receptor fluid of about 4 ml /1 min was selected. The experiments were carried out for 7 days at a temperature of 37°C. The released concentration of the model drug in the receptor solution was analyzed using UV-Vis spectroscopy (Perkin Elmer Company). Additionally, the following properties of the modified materials were studied: physicochemical, structural (FT-IR analysis), morphological (SEM analysis). Finally, the cytotoxicity tests using in vitro method were conducted. The obtained results exhibited that the dual release system allows for the gradual and prolonged delivery of the active substances, even up to 7 days.

Keywords: wound dressings, SA/PVA hydrogels, nanocarrier-drug system, USP4 method

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1033 Chloride Ion Channels Play a Role in Mediating Immune Response during Pseudomonas aeruginosa Infection

Authors: Hani M. Alothaid, Louise Robson, Richmond Muimo

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Cystic fibrosis (CF) is a disease that affects respiratory function and in EU it affects about 1 in 2,500 live births with an average 40-year life expectancy. This disease caused by mutations within the gene encoding the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) chloride channel leading to dysregulation of epithelial fluid transport and chronic lung inflammation, suggesting functional alterations of immune cells. In airways, CFTR been found to form a functional complex with S100A10 and AnxA2 in a cAMP/PKA dependent manner. The multiprotein complex of AnxA2-S100A10 and CFTR is also regulated by calcineurin. The aim of this study was i) to investigate whether chloride ion (Cl−) channels are activated by Pseudomonas aeruginosa lipopolysaccharide (LPS from PA), ii) if this activation is regulated by cAMP/PKA/calcineurin pathway and iii) to investigate the role of LPS-activated Cl− channels in the release of pro-inflammatory cytokines by immune cells. Human peripheral blood monocytes were used in the study. Whole-cell patch records showed that LPS from PA can activate Cl− channels, including CFTR and outwardly-rectifying Cl− channel (ORCC). This activation appears to require an intact PKA/calcineurin signalling pathway. The Gout in the presence of LPS was significantly inhibited by diisothiocyanatostilbene-disulfonic acid (DIDS), an ORCC blocker (p<0.001). The Gout was further suppressed by CFTR(inh)-172, a specific inhibitor for CFTR channels (p<0.001). Monocytes pre-incubated with PKA inhibitor or calcineurin inhibitor before stimulated with LPS from PA that were resulted in DIDS and CFTR(inh)-172 insensitive currents. Activation of both ORCC and CFTR was however, observed in response to monocytes exposure to LPS. Additionally, ELISA showed that the CFTR and ORCC play a role in mediating the release of pro-inflammatory cytokines such as IL-1β upon exposure of monocytes to LPS. However, this secretion was significantly inhibited due to CFTR and ORCC inhibition. However, Cl− may play a role in IL-1β release independent of cAMP/PKA/calcineurin signalling due to the enhancement of IL-1β secretion even when cAMP/PKA/calcineurin pathway was inhibited. In conclusion, our data confirmed that LPS from PA activates Cl− channels in human peripheral blood monocytes. Our data also confirmed that Cl− channels were involved in IL-1β release in monocytes upon exposure to LPS. However, it has been found that PKA and calcineurin does not seem to influence the Cl− dependent cytokine release.

Keywords: cystic fibrosis, CFTR, Annexin A2, S100A10, PP2B, PKA, outwardly-rectifying Cl− channel, Pseudomonas aeruginosa

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1032 Floating Oral in Situ Gelling System of Anticancer Drug

Authors: Umme Hani, Mohammed Rahmatulla, Mohammed Ghazwani, Ali Alqahtani, Yahya Alhamhoom

Abstract:

Background and introduction: Neratinib is a potent anticancer drug used for the treatment of breast cancer. It is poorly soluble at higher pH, which tends to minimize the therapeutic effects in the lower gastrointestinal tract (GIT) leading to poor bioavailability. An attempt has been made to prepare and develop a gastro-retentive system of Neratinib to improve the drug bioavailability in the GIT by enhancing the gastric retention time. Materials and methods: In the present study a three-factor at two-level (23) factorial design based optimization was used to inspect the effects of three independent variables (factors) such as sodium alginate (A), sodium bicarbonate (B) and sodium citrate (C) on the dependent variables like in vitro gelation, in vitro floating, water uptake and percentage drug release. Results: All the formulations showed pH in the range 6.7 ±0.25 to 7.4 ±0.24, percentage drug content was observed to be 96.3±0.27 to 99.5 ±0.28%, in vitro gelation observed as gelation immediate remains for an extended period. Percentage of water uptake was in the range between 9.01±0.15 to 31.01±0.25%, floating lag time was estimated form 7±0.39 to 57±0.36 sec. F4 and F5 showed floating even after 12hrs. All formulations showed a release of around 90% drug release within 12hr. It was observed that the selected independent variables affect the dependent variables. Conclusion: The developed system may be a promising and alternative approach to augment gastric retention of drugs and enhances the therapeutic efficacy of the drug.

Keywords: neratinib, 2³ factorial design, sodium alginate, floating, in situ gelling system

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1031 Inhibitory Effect on TNF-Alpha Release of Dioscorea membranacea and Its Compounds

Authors: Arunporn Itharat, Srisopa Ruangnoo, Pakakrong Thongdeeying

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The rhizomes of Dioscorea membranacea (DM) has long been used in Thai Traditional medicine to treat cancer and inflammatory conditions such as rheumatism. The objective of this study was to investigate anti-inflammatory activity by determining the inhibitory effect on LPS-induced TNF-α from RAW264.7 cells of crude extracts and pure isolated compounds from DM. Three known dihydrophenantrene compounds were isolated by a bioassay guided isolation method from DM ethanolic extract [2,4 dimethoxy-5,6-dihydroxy-9,10-dihydrophenanthrene (1) and 5-hydroxy-2,4,6-trimethoxy-9,10-dihydrophenanthrene(2) and 5,6,2 -trihydroxy 3,4-methoxy, 9,10- dihydrophenanthrene (3)]. 1 showed the highest inhibitory effect on PGE2, followed by 3 and 1 (IC50 = 2.26, 4.97 and >20 μg/ml or 8.31,17.25 and > 20 µM respectively). These findings suggest that this plant showed anti-inflamatory effects by displaying an inhibitory effect on TNF-α release, hence, this result supports the usage of Thai traditional medicine to treat inflammation related diseases.

Keywords: Dioscorea membranacea, anti-inflammatory activity, TNF-Alpha , dihidrophenantrene compound

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1030 Ordered Mesoporous Carbons of Different Morphology for Loading and Controlled Release of Active Pharmaceutical Ingredients

Authors: Aleksander Ejsmont, Aleksandra Galarda, Joanna Goscianska

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Smart porous carriers with defined structure and physicochemical properties are required for releasing the therapeutic drug with precise control of delivery time and location in the body. Due to their non-toxicity, ordered structure, chemical, and thermal stability, mesoporous carbons can be considered as modern carriers for active pharmaceutical ingredients (APIs) whose effectiveness needs frequent dosing algorithms. Such an API-carrier system, if programmed precisely, may stabilize the pharmaceutical and increase its dissolution leading to enhanced bioavailability. The substance conjugated with the material, through its prior adsorption, can later be successfully applied internally to the organism, as well as externally if the API release is feasible under these conditions. In the present study, ordered mesoporous carbons of different morphologies and structures, prepared by hard template method, were applied as carriers in the adsorption and controlled release of active pharmaceutical ingredients. In the first stage, the carbon materials were synthesized and functionalized with carboxylic groups by chemical oxidation using ammonium persulfate solution and then with amine groups. Materials obtained were thoroughly characterized with respect to morphology (scanning electron microscopy), structure (X-ray diffraction, transmission electron microscopy), characteristic functional groups (FT-IR spectroscopy), acid-base nature of surface groups (Boehm titration), parameters of the porous structure (low-temperature nitrogen adsorption) and thermal stability (TG analysis). This was followed by a series of tests of adsorption and release of paracetamol, benzocaine, and losartan potassium. Drug release experiments were performed in the simulated gastric fluid of pH 1.2 and phosphate buffer of pH 7.2 or 6.8 at 37.0 °C. The XRD patterns in the small-angle range and TEM images revealed that functionalization of mesoporous carbons with carboxylic or amine groups leads to the decreased ordering of their structure. Moreover, the modification caused a considerable reduction of the carbon-specific surface area and pore volume, but it simultaneously resulted in changing their acid-base properties. Mesoporous carbon materials exhibit different morphologies, which affect the host-guest interactions during the adsorption process of active pharmaceutical ingredients. All mesoporous carbons show high adsorption capacity towards drugs. The sorption capacity of materials is mainly affected by BET surface area and the structure/size matching between adsorbent and adsorbate. Selected APIs are linked to the surface of carbon materials mainly by hydrogen bonds, van der Waals forces, and electrostatic interactions. The release behavior of API is highly dependent on the physicochemical properties of mesoporous carbons. The release rate of APIs could be regulated by the introduction of functional groups and by changing the pH of the receptor medium. Acknowledgments—This research was supported by the National Science Centre, Poland (project SONATA-12 no: 2016/23/D/NZ7/01347).

Keywords: ordered mesoporous carbons, sorption capacity, drug delivery, carbon nanocarriers

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1029 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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1028 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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1027 Heat Transfer Studies for LNG Vaporization During Underwater LNG Releases

Authors: S. Naveen, V. Sivasubramanian

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A modeling theory is proposed to consider the vaporization of LNG during its contact with water following its release from an underwater source. The spillage of LNG underwater can lead to a decrease in the surface temperature of water and subsequent freezing. This can in turn affect the heat flux distribution from the released LNG onto the water surrounding it. The available models predict the rate of vaporization considering the surface of contact as a solid wall, and considering the entire phenomena as a solid-liquid operation. This assumption greatly under-predicted the overall heat transfer on LNG water interface. The vaporization flux would first decrease during the film boiling, followed by an increase during the transition boiling and a steady decrease during the nucleate boiling. A superheat theory is introduced to enhance the accuracy in the prediction of the heat transfer between LNG and water. The work suggests that considering the superheat theory can greatly enhance the prediction of LNG vaporization on underwater releases and also help improve the study of overall thermodynamics.

Keywords: evaporation rate, heat transfer, LNG vaporization, underwater LNG release

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1026 Characterization of Calcium-Signalling Mediated by Human GPR55 Expressed in HEK293 Cells

Authors: Yousuf M. Al Suleimani, Robin Hiley

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The endogenous phospholipid lysophosphatidylinositol (LPI) was recently identified as a novel ligand for the G protein-coupled receptor 55 (GPR55) and an inducer of intracellular Ca2+ [Ca2+]i release. This study attempts to characterize Ca2+ signals provoked by LPI in HEK293 cells engineered to stably express human GPR55 and to test cannabinoid ligand activity at GPR55. The study shows that treatment with LPI stimulates a sustained, oscillatory Ca2+ release. The response is characterized by an initial rapid rise, which is mediated by the Gαq-PLC-IP3 pathway, and this is followed by prolonged oscillations that require RhoA activation. Ca2+ oscillations are initiated by intracellular mechanisms and extracellular Ca2+ is only required to replenish Ca2+ lost from the cytoplasm. Analysis of cannabinoid ligand activity at GPR55 revealed no clear effect of the endocannabinoid anandamide, however, rimonabant and the CB1 receptor antagonist AM251 evoked GPR55-mediated [Ca2+]i. Thus, LPI is likely to be a key plasma membrane mediator of signaling events and changes in gene expression through GPR55 activation.

Keywords: lysophosphatidylinositol, calcium, GPR55, cannabinoid

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1025 Development and Optimization of Colon Targeted Drug Delivery System of Ayurvedic Churna Formulation Using Eudragit L100 and Ethyl Cellulose as Coating Material

Authors: Anil Bhandari, Imran Khan Pathan, Peeyush K. Sharma, Rakesh K. Patel, Suresh Purohit

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The purpose of this study was to prepare time and pH dependent release tablets of Ayurvedic Churna formulation and evaluate their advantages as colon targeted drug delivery system. The Vidangadi Churna was selected for this study which contains Embelin and Gallic acid. Embelin is used in Helminthiasis as therapeutic agent. Embelin is insoluble in water and unstable in gastric environment so it was formulated in time and pH dependent tablets coated with combination of two polymers Eudragit L100 and ethyl cellulose. The 150mg of core tablet of dried extract and lactose were prepared by wet granulation method. The compression coating was used in the polymer concentration of 150mg for both the layer as upper and lower coating tablet was investigated. The results showed that no release was found in 0.1 N HCl and pH 6.8 phosphate buffers for initial 5 hours and about 98.97% of the drug was released in pH 7.4 phosphate buffer in total 17 hours. The in vitro release profiles of drug from the formulation could be best expressed first order kinetics as highest linearity (r2= 0.9943). The results of the present study have demonstrated that the time and pH dependent tablets system is a promising vehicle for preventing rapid hydrolysis in gastric environment and improving oral bioavailability of Embelin and Gallic acid for treatment of Helminthiasis.

Keywords: embelin, gallic acid, Vidangadi Churna, colon targeted drug delivery

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1024 Concanavaline a Conjugated Bacterial Polyester Based PHBHHx Nanoparticles Loaded with Curcumin for the Ovarian Cancer Therapy

Authors: E. Kilicay, Z. Karahaliloglu, B. Hazer, E. B. Denkbas

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In this study, we have prepared concanavaline A (ConA) functionalized curcumin (CUR) loaded PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) nanoparticles as a novel and efficient drug delivery system. CUR is a promising anticancer agent for various cancer types. The aim of this study was to evaluate therapeutic potential of curcumin loaded PHBHHx nanoparticles (CUR-NPs) and concanavaline A conjugated curcumin loaded NPs (ConA-CUR NPs) for ovarian cancer treatment. ConA was covalently connected to the carboxylic group of nanoparticles by EDC/NHS activation method. In the ligand attachment experiment, the binding capacity of ConA on the surface of NPs was found about 90%. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis showed that the prepared nanoparticles were smooth and spherical in shape. The size and zeta potential of prepared NPs were about 228±5 nm and −21.3 mV respectively. ConA-CUR NPs were characterized by FT-IR spectroscopy which confirmed the existence of CUR and ConA in the nanoparticles. The entrapment and loading efficiencies of different polymer/drug weight ratios, 1/0.125 PHBHHx/CUR= 1.25CUR-NPs; 1/0.25 PHBHHx/CUR= 2.5CUR-NPs; 1/0.5 PHBHHx/CUR= 5CUR-NPs, ConA-1.25CUR NPs, ConA-2.5CUR NPs and ConA-5CUR NPs were found to be ≈ 68%-16.8%; 55%-17.7 %; 45%-33.6%; 70%-15.7%; 60%-17%; 51%-30.2% respectively. In vitro drug release showed that the sustained release of curcumin was observed from CUR-NPs and ConA-CUR NPs over a period of 19 days. After binding of ConA, the release rate was slightly increased due to the migration of curcumin to the surface of the nanoparticles and the matrix integrities was decreased because of the conjugation reaction. This functionalized nanoparticles demonstrated high drug loading capacity, sustained drug release profile, and high and long term anticancer efficacy in human cancer cell lines. Anticancer activity of ConA-CUR NPs was proved by MTT assay and reconfirmed by apoptosis and necrosis assay. The anticancer activity of ConA-CUR NPs was measured in ovarian cancer cells (SKOV-3) and the results revealed that the ConA-CUR NPs had better tumor cells decline activity than free curcumin. The nacked nanoparticles have no cytotoxicity against human ovarian carcinoma cells. Thus the developed functionalized nanoformulation could be a promising candidate in cancer therapy.

Keywords: curcumin, curcumin-PHBHHx nanoparticles, concanavalin A, concanavalin A-curcumin PHBHHx nanoparticles, PHBHHx nanoparticles, ovarian cancer cell

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1023 Effectiveness of Myofascial Release Technique in Treatment of Sacroiliac Joint Hypo-Mobility in Postnatal Women

Authors: Ahmed A. Abd El Rahim, Mohamed M. M. Essa, Magdy M. A. Shabana, Said A. Mohamed, Mohamed Ibrahim Mabrouk

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Background: Sacroiliac joint (SIJ) dysfunction is considered the main cause of pregnancy-related back pain, which may continue to persist postnatally. Myofascial release technique (MFR) is an application of low-intensity, prolonged stretch to myofascial structures to improve function by increasing the sliding properties of restricted myofascial tissues. Purpose: This study was designed to investigate the effect of MFR on postnatal SIJ hypo-mobility. Materials and Methods: Fifty postnatal women complaining of SIJ hypo-mobility participated in this study. Their ages ranged from 26 to 35 yrs., and their body mass index (BMI) didn`t exceed 30 kg/m2. They were randomly assigned to two equal groups, group A (Gr. A) and group B (Gr. B). Both groups received three sessions per week for eight successive weeks. Gr. A received a traditional physical therapy program, while Gr. B received a traditional physical therapy program in addition to MFR. Doppler imaging of vibration was utilized to measure SIJ mobility pre- and post-intervention, and an electronic digital goniometer was used to measure back flexion and extension Range of motion. Results: Findings revealed a statistical improvement in post-intervention values of SIJ mobility in addition to trunk flexion and extension ROM in Gr. B compared to Gr. A (P<0.001). Conclusion: Adding MFR to traditional physical therapy programs is highly recommended in the treatment of SIJ hypo-mobility in postnatal women.

Keywords: sacroiliac hypo-mobility, sacroiliac dysfunction, myofascial release technique, traditional physical therapy, postnatal

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1022 Comparative Effect of Self-Myofascial Release as a Warm-Up Exercise on Functional Fitness of Young Adults

Authors: Gopal Chandra Saha, Sumanta Daw

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Warm-up is an essential component for optimizing performance in various sports before a physical fitness training session. This study investigated the immediate comparative effect of Self-Myofascial Release through vibration rolling (VR), non-vibration rolling (NVR), and static stretching as a part of a warm-up treatment on the functional fitness of young adults. Functional fitness is a classification of training that prepares the body for real-life movements and activities. For the present study 20male physical education students were selected as subjects. The age of the subjects was ranged from 20-25 years. The functional fitness variables undertaken in the present study were flexibility, muscle strength, agility, static and dynamic balance of the lower extremity. Each of the three warm-up protocol was administered on consecutive days, i.e. 24 hr time gap and all tests were administered in the morning. The mean and SD were used as descriptive statistics. The significance of statistical differences among the groups was measured by applying ‘F’-test, and to find out the exact location of difference, Post Hoc Test (Least Significant Difference) was applied. It was found from the study that only flexibility showed significant difference among three types of warm-up exercise. The observed result depicted that VR has more impact on myofascial release in flexibility in comparison with NVR and stretching as a part of warm-up exercise as ‘p’ value was less than 0.05. In the present study, within the three means of warm-up exercises, vibration roller showed better mean difference in terms of NVR, and static stretching exercise on functional fitness of young physical education practitioners, although the results were found insignificant in case of muscle strength, agility, static and dynamic balance of the lower extremity. These findings suggest that sports professionals and coaches may take VR into account for designing more efficient and effective pre-performance routine for long term to improve exercise performances. VR has high potential to interpret into an on-field practical application means.

Keywords: self-myofascial release, functional fitness, foam roller, physical education

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1021 Corrosion Behavior of Fe-Ni-Cr and Zr Alloys in Supercritical Water Reactors

Authors: Igor Svishchev, Kashif Choudhry

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Progress in advanced energy technologies is not feasible without understanding how engineering materials perform under extreme environmental conditions. The corrosion behaviour of Fe-Ni-Cr and Zr alloys has been systematically examined under high-temperature and supercritical water flow conditions. The changes in elemental release rate and dissolved gas concentration provide valuable insights into the mechanism of passivation by forming oxide films. A non-intrusive method for monitoring the extent of surface oxidation based on hydrogen release rate has been developed. This approach can be used for the on-line monitoring corrosion behavior of reactor materials without the need to interrupt the flow and remove corrosion coupons. Surface catalysed thermochemical reactions may generate sufficient hydrogen to have an effect on the accumulation of oxidizing species generated by radiolytic processes in the heat transport systems of the supercritical water cooled nuclear reactor.

Keywords: high-temperature corrosion, non-intrusive monitoring, reactor materials, supercritical water

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1020 Formulation and Evaluation of Colon-Specific Drug Delivery System of Zaltoprofen

Authors: Surajj Sarode, G. P. Vadnere, G. Vidya Sagar

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Compression coating is one of the strategies for delivering drug to the colon based on Gastrointestinal PH and transit time concept. The main aim of these formulations to develop rapidly disintegrating Zaltoprofen core tablets compression-coated with a mixture of time-dependent hydrophilic swellable polymer HPMC K 15 and PH responsive soluble polymer Chitosan and Guar gum in different ratios. The effect of the proportion of HPMC, Chitosan and Guar gum in the coat on premature drug release in upper part (Stomach and small intestine) of GIT and the amount of drug release in colon target area was studied. The formulations are carried out by using Direct Compression method. Sodium starch Glycolate used for rapid disintegration. FTIR used for Drug-Polymer Interaction studies. The prepared tablets were evaluated for hardness, thickness, friability, in-vitro disintegration, in-Vitro dissolution and in-vitro kinetic study.

Keywords: zaltoprofen, chitosan, formulation, drug delivery

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1019 Experimental Investigation on the Fire Performance of Corrugated Sandwich Panels made from Renewable Material

Authors: Avishek Chanda, Nam Kyeun Kim, Debes Bhattacharyya

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The use of renewable substitutes in various semi-structural and structural applications has experienced an increase since the last few decades. Sandwich panels have been used for many decades, although research on understanding the effects of the core structures on the panels’ fire-reaction properties is limited. The current work investigates the fire-performance of a corrugated sandwich panel made from renewable, biodegradable, and sustainable material, plywood. The bench-scale fire testing apparatus, cone-calorimeter, was employed to evaluate the required fire-reaction properties of the sandwich core in a panel configuration, with three corrugated layers glued together with face-sheets under a heat irradiance of 50 kW/m2. The study helped in documenting a unique heat release trend associated with the fire performance of the 3-layered corrugated sandwich panels and in understanding the structural stability of the samples in the event of a fire. Furthermore, the total peak heat release rate was observed to be around 421 kW/m2, which is significantly low compared to many polymeric materials in the literature. The total smoke production was also perceived to be very limited compared to other structural materials, and the total heat release was also nominal. The time to ignition of 21.7 s further outlined the advantages of using the plywood component since polymeric composites, even with flame-retardant additives, tend to ignite faster. Overall, the corrugated plywood sandwich panels had significant fire-reaction properties and could have important structural applications. The possible use of structural panels made from bio-degradable material opens a new avenue for the use of similar structures in sandwich panel preparation.

Keywords: corrugated sandwich panel, fire-reaction properties, plywood, renewable material

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1018 Preparation and In vitro Characterization of Nanoparticle Hydrogel for Wound Healing

Authors: Rajni Kant Panik

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The aim of the present study was to develop and evaluate mupirocin loaded nanoparticle incorporated into hydrogel as an infected wound healer. Incorporated Nanoparticle in hydrogel provides a barrier that effectively prevents the contamination of the wound and further progression of infection to deeper tissues. Hydrogel creates moist healing environment on wound space with good fluid absorbance. Nanoparticles were prepared by double emulsion solvent evaporation method using different ratios of PLGA polymer and the hydrogels was developed using sodium alginate and gelatin. Further prepared nanoparticles were then incorporated into the hydrogels. The formulations were characterized by FT-IR and DSC for drug and polymer compatibility and surface morphology was studied by TEM. Nanoparticle hydrogel were evaluated for their size, shape, encapsulation efficiency and for in vitro studies. The FT-IR and DSC confirmed the absence of any drug polymer interaction. The average size of Nanoparticle was found to be in range of 208.21-412.33 nm and shape was found to be spherical. The maximum encapsulation efficiency was found to be 69.03%. The in vitro release profile of Nanoparticle incorporated hydrogel formulation was found to give sustained release of drug. Antimicrobial activity testing confirmed that encapsulated drug preserve its effectiveness. The stability study confirmed that the formulation prepared were stable. Present study complements our finding that mupirocin loaded Nanoparticle incorporated into hydrogel has the potential to be an effective and safe novel addition for the release of mupirocin in sustained manner, which may be a better option for the management of wound. These finding also supports the progression of antibiotic via hydrogel delivery system is a novel topical dosage form for the management of wound.

Keywords: hydrogel, nanoparticle, PLGA, wound healing

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1017 Antibacterial Activity of Nisin: Comparison the Role of Free and Encapsulated Nisin to Control Staphylococcus Aureus Inoculated in Minced Beef

Authors: Zh. Ghasemi, S. Nouri Saeedlou, A. Ghasemi, SL. Nasiri, P. Ayremlou, P. Mahasti

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The use of nisin is successfully used as antibacterial agent in various food products. Although the conclusions of the previous studies were that nisin is not very effective in meat environments. The reduced antimicrobial efficacy of nisin when applied in food has been frequently observed. The aim of this study is to evaluate the potential of free and encapsulated nisin to inhibit the growth of staphylococcus aureus in minced beef. The minimum inhibitory concentration (MIC) of nisin is determined against S. aureus using the agar dilution method. Nisin is encapsulated by spray drying, and encapsulation efficiency, mass yield and total solids content values are 47.79%, 61%, and 96.41 respectively. The study in vitro release kinetics shows highest release of nisin from zein capsules is obtained after 72 hour. This work shows that an appropriate delivery system is necessary to obtain desirable effect of nisin in meat and meat product.

Keywords: nisin, encapsulation, Staphylococcus aureus, minced beef, antibacterial activity

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1016 Formulation and Evaluation of Curcumin-Zn (II) Microparticulate Drug Delivery System for Antimalarial Activity

Authors: M. R. Aher, R. B. Laware, G. S. Asane, B. S. Kuchekar

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Objective: Studies have shown that a new combination therapy with Artemisinin derivatives and curcumin is unique, with potential advantages over known ACTs. In present study an attempt was made to prepare microparticulate drug delivery system of Curcumin-Zn complex and evaluate it in combination with artemether for antimalarial activity. Material and method: Curcumin Zn complex was prepared and encapsulated using sodium alginate. Microparticles thus obtained are further coated with various enteric polymers at different coating thickness to control the release. Microparticles are evaluated for encapsulation efficiency, drug loading and in vitro drug release. Roentgenographic Studies was conducted in rabbits with BaSO 4 tagged formulation. Optimized formulation was screened for antimalarial activity using P. berghei-infected mice survival test and % paracetemia inhibition, alone (three oral dose of 5mg/day) and in combination with arthemether (i.p. 500, 1000 and 1500µg). Curcumin-Zn(II) was estimated in serum after oral administration to rats by using spectroflurometry. Result: Microparticles coated with Cellulose acetate phthalate showed most satisfactory and controlled release with 479 min time for 60% drug release. X-ray images taken at different time intervals confirmed the retention of formulation in GI tract. Estimation of curcumin in serum by spectroflurometry showed that drug concentration is maintained in the blood for longer time with tmax of 6 hours. The survival time (40 days post treatment) of mice infected with P. berghei was compared to survival after treatment with either Curcumin-Zn(II) microparticles artemether combination, curcumin-Zn complex and artemether. Oral administration of Curcumin-Zn(II)-artemether prolonged the survival of P.berghei-infected mice. All the mice treated with Curcumin-Zn(II) microparticles (5mg/day) artemether (1000µg) survived for more than 40 days and recovered with no detectable parasitemia. Administration of Curcumin-Zn(II) artemether combination reduced the parasitemia in mice by more than 90% compared to that in control mice for the first 3 days after treatment. Conclusion: Antimalarial activity of the curcumin Zn-artemether combination was more pronounced than mono therapy. A single dose of 1000µg of artemether in curcumin-Zn combination gives complete protection in P. berghei-infected mice. This may reduce the chances of drug resistance in malaria management.

Keywords: formulation, microparticulate drug delivery, antimalarial, pharmaceutics

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1015 Polymeric Sustained Biodegradable Patch Formulation for Wound Healing

Authors: Abhay Asthana, Gyati Shilakari Asthana

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It’s the patient compliance and stability in combination with controlled drug delivery and biocompatibility that forms the core feature in present research and development of sustained biodegradable patch formulation intended for wound healing. The aim was to impart sustained degradation, sterile formulation, significant folding endurance, elasticity, biodegradability, bio-acceptability and strength. The optimized formulation was developed using component including polymers including Hydroxypropyl methyl cellulose, Ethylcellulose, and Gelatin, and Citric Acid PEG Citric acid (CPEGC) triblock dendrimers and active Curcumin. Polymeric mixture dissolved in geometric order in suitable medium through continuous stirring under ambient conditions. With continued stirring Curcumin was added with aid of DCM and Methanol in optimized ratio to get homogenous dispersion. The dispersion was sonicated with optimum frequency and for given time and later casted to form a patch form. All steps were carried out under under strict aseptic conditions. The formulations obtained in the acceptable working range were decided based on thickness, uniformity of drug content, smooth texture and flexibility and brittleness. The patch kept on stability using butter paper in sterile pack displayed folding endurance in range of 20 to 23 times without any evidence of crack in an optimized formulation at room temperature (RT) (24 ± 2°C). The patch displayed acceptable parameters after stability study conducted in refrigerated conditions (8±0.2°C) and at RT (24 ± 2°C) upto 90 days. Further, no significant changes were observed in critical parameters such as elasticity, biodegradability, drug release and drug content during stability study conducted at RT 24±2°C for 45 and 90 days. The drug content was in range 95 to 102%, moisture content didn’t exceeded 19.2% and patch passed the content uniformity test. Percentage cumulative drug release was found to be 80% in 12h and matched the biodegradation rate as drug release with correlation factor R2>0.9. The biodegradable patch based formulation developed shows promising results in terms of stability and release profiles.

Keywords: sustained biodegradation, wound healing, polymers, stability

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1014 Deployed Confidence: The Testing in Production

Authors: Shreya Asthana

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Testers know that the feature they tested on stage is working perfectly in production only after release went live. Sometimes something breaks in production and testers get to know through the end user’s bug raised. The panic mode starts when your staging test results do not reflect current production behavior. And you started doubting your testing skills when finally the user reported a bug to you. Testers can deploy their confidence on release day by testing on production. Once you start doing testing in production, you will see test result accuracy because it will be running on real time data and execution will be a little faster as compared to staging one due to elimination of bad data. Feature flagging, canary releases, and data cleanup can help to achieve this technique of testing. By this paper it will be easier to understand the steps to achieve production testing before making your feature live, and to modify IT company’s testing procedure, so testers can provide the bug free experience to the end users. This study is beneficial because too many people think that testing should be done in staging but not in production and now this is high time to pull out people from their old mindset of testing into a new testing world. At the end of the day, it all just matters if the features are working in production or not.

Keywords: bug free production, new testing mindset, testing strategy, testing approach

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1013 Design and Development of Mucoadhesive Buccal Film Bearing Itraconazole

Authors: Yuvraj Singh Dangi, Kamta Prasad Namdeo, Surendra Bodhake

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The purpose of this research was to develop and evaluate mucoadhesive films for buccal administration of itraconazole using film-forming and mucoashesive polymers. Buccal films of chitosan bearing Itraconazole were prepared by solvent casting technique. The films have been evaluated in terms of film weight, thickness, density, surface pH, FTIR, X-ray diffraction analysis, bioadhesion, swelling properties, and in vitro drug release studies. It was found that film formulations of 2 cm2 size having weight in the range of 204 ± 0.76 to 223 ± 2.09 mg and film thickness were in the range of 0.44 ± 0.11 to 0.57 ± 0.19 mm. Density of the films was found to be 0.102 to 0.126 g/ml. Drug content was found to be uniform in the range of 8.23 ± 0.07 to 8.73 ± 0.09 mg/cm2 for formulation A1 to A4. Maximum bioadhesion force was recorded for HPMC buccal films (A2) i.e. 0.57 ± 0.47 as compared to other films. In vitro residence time was in range of 1.7 ± 0.12 to 7.65 ± 0.15 h. The drug release studies show that formulations follow non-fickian diffusion. These mucoadhesive formulations could offer many advantages in comparison to traditional treatments.

Keywords: biovariability, buccal patches, itraconazole, Mucoadhesion

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1012 Simulation of Optimum Sculling Angle for Adaptive Rowing

Authors: Pornthep Rachnavy

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The purpose of this paper is twofold. First, we believe that there are a significant relationship between sculling angle and sculling style among adaptive rowing. Second, we introduce a methodology used for adaptive rowing, namely simulation, to identify effectiveness of adaptive rowing. For our study we simulate the arms only single scull of adaptive rowing. The method for rowing fastest under the 1000 meter was investigated by study sculling angle using the simulation modeling. A simulation model of a rowing system was developed using the Matlab software package base on equations of motion consist of many variation for moving the boat such as oars length, blade velocity and sculling style. The boat speed, power and energy consumption on the system were compute. This simulation modeling can predict the force acting on the boat. The optimum sculling angle was performing by computer simulation for compute the solution. Input to the model are sculling style of each rower and sculling angle. Outputs of the model are boat velocity at 1000 meter. The present study suggests that the optimum sculling angle exist depends on sculling styles. The optimum angle for blade entry and release with respect to the perpendicular through the pin of the first style is -57.00 and 22.0 degree. The optimum angle for blade entry and release with respect to the perpendicular through the pin of the second style is -57.00 and 22.0 degree. The optimum angle for blade entry and release with respect to the perpendicular through the pin of the third style is -51.57 and 28.65 degree. The optimum angle for blade entry and release with respect to the perpendicular through the pin of the fourth style is -45.84 and 34.38 degree. A theoretical simulation for rowing has been developed and presented. The results suggest that it may be advantageous for the rowers to select the sculling angles proper to sculling styles. The optimum sculling angles of the rower depends on the sculling styles made by each rower. The investigated of this paper can be concludes in three directions: 1;. There is the optimum sculling angle in arms only single scull of adaptive rowing. 2. The optimum sculling angles depend on the sculling styles. 3. Computer simulation of rowing can identify opportunities for improving rowing performance by utilizing the kinematic description of rowing. The freedom to explore alternatives in speed, thrust and timing with the computer simulation will provide the coach with a tool for systematic assessments of rowing technique In addition, the ability to use the computer to examine the very complex movements during rowing will help both the rower and the coach to conceptualize the components of movements that may have been previously unclear or even undefined.

Keywords: simulation, sculling, adaptive, rowing

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1011 The Influence of Thomson Effect on the Performance of N-Type Skutterudite Thermoelement

Authors: Anbang Liu, Huaqing Xie, Zihua Wu, Xiaoxiao Yu, Yuanyuan Wang

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Due to the temperature-dependence and mutual coupling of thermoelectric parameters, the Thomson effect always exists, which is derived from temperature gradients during thermoelectric conversion. The synergistic effect between the Thomson effect and non-equilibrium heat transport of charge carriers leads to local heat absorption or release in thermoelements, thereby affecting its power generation performance and conversion efficiency. This study verified and analyzed the influence and mechanism of the Thomson effect on N-type skutterudite thermoelement through quasi-steady state testing under approximate vacuum conditions. The results indicate the temperature rise/fall of N-type thermoelement at any position is affected by Thomson heat release/absorption. Correspondingly, the Thomson effect also contributes advantageously/disadvantageously to the output power of N-type skutterudite thermoelement when the Thomson coefficients are positive/negative. In this work, the output power can be promoted or decreased maximally by more than 27% due to the presence of Thomson heat when the absolute value of the Thomson coefficient is around 36 μV/℃.

Keywords: Thomson effect, heat transport, thermoelectric conversion, numerical simulation

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1010 Formulation and Evaluation of Silibilin Loaded PLGA Nanoparticles for Cancer Therapy

Authors: Priya Patel, Paresh Patel, Mihir Raval

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Silibinin, a flavanone as an antimicrotubular agent used in the treatment of cancer, was encapsulated in nanoparticles (NPs) of poly (lactide-co-glycolide) (PLGA) polymer using the spray-drying technique. The effects of various experimental parameters were optimized by box-behnken experimental design. Production yield, encapsulation efficiency and dissolution study along with characterization by scanning electron microscopy, DSC, FTIR followed by bioavailability study. Particle size and zeta potential were evaluated by using zetatrac particle size analyzer. Experimental design it was evaluated that inlet temperature and polymer concentration influence on the drug release. Feed flow rate impact on particle size. Results showed that spray drying technique yield 149 nm indicate nanosize range. The small size of the nanoparticle resulted in an enhanced cellular entry and greater bioavailability. Entrapment efficiency was found between 89.35% and 98.36%. Zeta potential shows good stability index of nanoparticle formulation. The in vitro release studies indicated the silibinin loaded PLGA nanoparticles provide controlled drug release over a period of 32 h. Pharmacokinetic studies demonstrated that after oral administration of silibinin-loaded PLGA nanoparticles to rats at a dose of 10 mg/kg, relative bioavailability was enhanced about 8.85-fold, compared to silibinin suspension as control hence, this investigation demonstrated the potential of the experimental design in understanding the effect of the formulation variables on the quality of silibinin loaded PLGA nanoparticles. These results describe an effective strategy of silibinin loaded PLGA nanoparticles and might provide a promising approach against the cancer.

Keywords: silibinin, cancer, nanoparticles, PLGA, bioavailability

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1009 Performance Evaluation of a Minimum Mean Square Error-Based Physical Sidelink Share Channel Receiver under Fading Channel

Authors: Yang Fu, Jaime Rodrigo Navarro, Jose F. Monserrat, Faiza Bouchmal, Oscar Carrasco Quilis

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Cellular Vehicle to Everything (C-V2X) is considered a promising solution for future autonomous driving. From Release 16 to Release 17, the Third Generation Partnership Project (3GPP) has introduced the definitions and services for 5G New Radio (NR) V2X. Experience from previous generations has shown that establishing a simulator for C-V2X communications is an essential preliminary step to achieve reliable and stable communication links. This paper proposes a complete framework of a link-level simulator based on the 3GPP specifications for the Physical Sidelink Share Channel (PSSCH) of the 5G NR Physical Layer (PHY). In this framework, several algorithms in the receiver part, i.e., sliding window in channel estimation and Minimum Mean Square Error (MMSE)-based equalization, are developed. Finally, the performance of the developed PSSCH receiver is validated through extensive simulations under different assumptions.

Keywords: C-V2X, channel estimation, link-level simulator, sidelink, 3GPP

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1008 Biopolymer Nanoparticles Loaded with Calcium as a Source of Fertilizer

Authors: Erwin San Juan Martinez, Miguel Angel Aguilar Mendez, Manuel Sandoval Villa, Libia Iris Trejo Tellez

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Some nanomaterials may improve the vegetal growth in certain concentration intervals, and could be used as nanofertilizers in order to increase crops yield, and decreasing the environmental pollution due to non-controlled use of conventional fertilizers, therefore the present investigation’s objective was to synthetize and characterize gelatin nanoparticles loaded with calcium generated through pulverization technique and be used as nanofertilizers. To obtain these materials, a fractional factorial design 27-4 was used in order to evaluate the largest number of factors (concentration of Ca2+, temperature and agitation time of the solution and calcium concentration, drying temperature, and % spray) with a possible effect on the size, distribution and morphology of nanoparticles. For the formation of nanoparticles, a Nano Spray-Dryer B - 90® (Buchi, Flawil, Switzerland), equipped with a spray cap of 4 µm was used. Size and morphology of the obtained nanoparticles were evaluated using a scanning electron microscope (JOEL JSM-6390LV model; Tokyo, Japan) equipped with an energy dispersive x-ray X (EDS) detector. The total quantification of Ca2+ as well as its release by the nanoparticles was carried out in an equipment of induction atomic emission spectroscopy coupled plasma (ICP-ES 725, Agilent, Mulgrave, Australia). Of the seven factors evaluated, only the concentration of fertilizer, % spray and concentration of polymer presented a statistically significant effect on particle size. Micrographs of SEM from six of the eight conditions evaluated in this research showed particles separated and with a good degree of sphericity, while in the other two particles had amorphous morphology and aggregation. In all treatments, most of the particles showed smooth surfaces. The average size of smallest particle obtained was 492 nm, while EDS results showed an even distribution of Ca2+ in the polymer matrix. The largest concentration of Ca2+ in ICP was 10.5%, which agrees with the theoretical value calculated, while the release kinetics showed an upward trend within 24 h. Using the technique employed in this research, it was possible to obtain nanoparticles loaded with calcium, of good size, sphericity and with release controlled properties. The characteristics of nanoparticles resulted from manipulation of the conditions of synthesis which allow control of the size and shape of the particles, and provides the means to adapt the properties of the materials to an specific application.

Keywords: calcium, controlled release, gelatin, nano spraydryer, nanofertilizer

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1007 Stomach Specific Delivery of Andrographolide from Floating in Situ Gelling System

Authors: Pravina Gurjar, Bothiraja Pour, Vijay Kumbhar, Ganesh Dama

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Andrographolide (AG), a bioactive phytoconstituent, has a wider range of pharmacological action. However, due to the intestinal degradation, shows low oral bioavailability. The aim of the present work was to develop Floating In-situ gelling Gastro retentive System (FISGS) for AG in order to enhance its site specific absorption and minimize pH dependent hydrolysis in alkaline environment. Further to increase its therapeutic efficacy for peptic ulcer disease caused by H. pyroli. Gellan based floating in situ gelling system of AG were prepared by using sodium citrate and calcium carbonate. The 32 factorial designs was used to study the effect of gellan and calcium carbonate concentration (independent variables) on dependent variable such as viscosity, floating lag time and drug release. Developed system was evaluated for drug content, floating lag time, viscosity, and drug release studies. Drug content, viscosity, and floating lag time was found to be 81-99%, 67-117 Cps, and 3-5 sec, respectively. The obtained system showed good in vitro floating ability for more than 12 h using 0.1 N HCl as dissolution medium with initial burst release followed by the controlled zero order drug release up to 24 hrs. In vivo testing of FISGS of AG to rats demonstrated significant antiulcer activity that were evaluated by various parameters like pH, volume, total acidity, millimole equivalent of H+ ions/30 min, and protein content of gastric content. The densities of all the formulation batches were found to be near about 0.9 and floating duration above 12 hr. It was observed that with the increase in conc. of gellan there was increase in the viscosity of formulation but all formulations were in optimum range. The drug content of optimized batch was found to be 99.23. In histopathology study of stomach, the villi at the mucosal surface, the intercellular junction, the intestinal lumen were intact; no destruction of the epithelium, and submucosal gland in formulation treated and control group animals as compared to pure drug AG and standard ranitidine. Gellan-based in situ gastro retentive floating system could be advantageous in terms of increased bioavailability of AG to maintain an effective drug conc. in gastric fluid as well as in serum for longer period of time.

Keywords: andrographolide, floating drug delivery, in situ gelling system, gastroretentive system

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1006 Application of Low Frequency Ac Magnetic Field for Controlled Delivery of Drugs by Magnetic Nanoparticles

Authors: K. Yu Vlasova, M. A. Abakumov, H. Wishwarsao, M. Sokolsky, N. V. Nukolova, A. G. Majouga, Y. I. Golovin, N. L. Klyachko, A. V. Kabanov

Abstract:

Introduction:Nowadays pharmaceutical medicine is aimed to create systems for combined therapy, diagnostic, drug delivery and controlled release of active molecules to target cells. Magnetic nanoparticles (MNPs) are used to achieve this aim. MNPs can be applied in molecular diagnostics, magnetic resonance imaging (T1/T2 contrast agents), drug delivery, hyperthermia and could improve therapeutic effect of drugs. The most common drug containers, containing MNPs, are liposomes, micelles and polymeric molecules bonded to the MNPs surface. Usually superparamagnetic nanoparticles are used (the general diameter is about 5-6 nm) and all effects of high frequency magnetic field (MF) application are based on Neel relaxation resulting in heating of surrounded media. In this work we try to develop a new method to improve drug release from MNPs under super low frequency MF. We suppose that under low frequency MF exposures the Brown’s relaxation dominates and MNPs rotation could occur leading to conformation changes and release of bioactive molecules immobilized on MNPs surface.The aim of this work was to synthesize different systems with active drug (biopolymers coated MNPs nanoclusters with immobilized enzymes and doxorubicin (Dox) loaded magnetic liposomes/micelles) and investigate the effect of super low frequency MF on these drug containers. Methods: We have synthesized MNPs of magnetite with magnetic core diameter 7-12 nm . The MNPs were coated with block-copolymer of polylysine and polyethylene glycol. Superoxide dismutase 1 (SOD1) was electrostatically adsorbed on the surface of the clusters. Liposomes were prepared as follow: MNPs, phosphatidylcholine and cholesterol were dispersed in chloroform, dried to get film and then dispersed in distillated water, sonicated. Dox was added to the solution, pH was adjusted to 7.4 and excess of drug was removed by centrifugation through 3 kDa filters. Results: Polylysine coated MNPs formed nanosized clusters (as observed by TEM) with intensity average diameter of 112±5 nm and zeta potential 12±3 mV. After low frequency AC MF exposure we observed change of immobilized enzyme activity and hydrodynamic size of clusters. We suppose that the biomolecules (enzymes) are released from the MNPs surface followed with additional aggregation of complexes at the MF in medium. Centrifugation of the nanosuspension after AC MF exposures resulted in increase of positive charge of clusters and change in enzyme concentration in comparison with control sample without MF, thus confirming desorption of negatively charged enzyme from the positively charged surface of MNPs. Dox loaded magnetic liposomes had average diameter of 160±8 nm and polydispersity index (PDI) 0.25±0.07. Liposomes were stable in DW and PBS at pH=7.4 at 370C during a week. After MF application (10 min of exposure, 50 Hz, 230 mT) diameter of liposomes raised to 190±10 nm and PDI was 0.38±0.05. We explain this by destroying and/or reorganization of lipid bilayer, that leads to changes in release of drug in comparison with control without MF exposure. Conclusion: A new application of low frequency AC MF for drug delivery and controlled drug release was shown. Investigation was supported by RSF-14-13-00731 grant, K1-2014-022 grant.

Keywords: magnetic nanoparticles, low frequency magnetic field, drug delivery, controlled drug release

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1005 Antibacterial Nanofibrous Film Encapsulated with 4-terpineol/β-cyclodextrin Inclusion Complexes: Relative Humidity-Triggered Release and Shrimp Preservation Application

Authors: Chuanxiang Cheng, Tiantian Min, Jin Yue

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Antimicrobial active packaging enables extensive biological effects to improve food safety. However, the efficacy of antimicrobial packaging hinges on factors including the diffusion rate of the active agent toward the food surface, the initial content in the antimicrobial agent, and the targeted food shelf life. Among the possibilities of antimicrobial packaging design, an interesting approach involves the incorporation of volatile antimicrobial agents into the packaging material. In this case, the necessity for direct contact between the active packaging material and the food surface is mitigated, as the antimicrobial agent exerts its action through the packaging headspace atmosphere towards the food surface. However, it still remains difficult to achieve controlled and precise release of bioactive compounds to the specific target location with required quantity in food packaging applications. Remarkably, the development of stimuli-responsive materials for electrospinning has introduced the possibility of achieving controlled release of active agents under specific conditions, thereby yielding enduring biological effects. Relative humidity (RH) for the storage of food categories such as meat and aquatic products typically exceeds 90%. Consequently, high RH can be used as an abiotic trigger for the release of active agents to prevent microbial growth. Hence, a novel RH - responsive polyvinyl alcohol/chitosan (PVA/CS) composite nanofibrous film incorporated with 4-terpineol/β-cyclodextrin inclusion complexes (4-TA@β-CD ICs) was engineered by electrospinning that can be deposited as a functional packaging materials. The characterization results showed the thermal stability of the films was enhanced after the incorporation due to the hydrogen bonds between ICs and polymers. Remarkably, the 4 wt% 4-TA@β-CD ICs/PVA/CS film exhibited enhanced crystallinity, moderate hydrophilic (Water contact angle of 81.53°), light barrier property (Transparency of 1.96%) and water resistance (Water vapor permeability of 3.17 g mm/m2 h kPa). Moreover, this film also showed optimized mechanical performance with a Young’s modulus of 11.33 MPa, a tensile strength of 19.99 MPa and an elongation at break of 4.44 %. Notably, the antioxidant and antibacterial properties of this packaging material were significantly improved. The film demonstrated the half-inhibitory concentrations (IC50) values of 87.74% and 85.11% for scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2′-azinobis (3-ethylbenzothiazoline-6-sulfonic) (ABTS) free radicals, respectively, in addition to an inhibition efficiency of 65% against Shewanella putrefaciens, the characteristic bacteria in aquatic products. Most importantly, the film achieved controlled release of 4-TA under high 98% RH by inducing the plasticization of polymers caused by water molecules, swelling of polymer chains, and destruction of hydrogen bonds within the cyclodextrin inclusion complex. Consequently, low relative humidity is suitable for the preservation of nanofibrous film, while high humidity conditions typical in fresh food packaging environments effectively stimulated the release of active compounds in the film. This film with a long-term antimicrobial effect successfully extended the shelf life of Litopenaeus vannamei shrimp to 7 days at 4 °C. This attractive design could pave the way for the development of new food packaging materials.

Keywords: controlled release, electrospinning, nanofibrous film, relative humidity–responsive, shrimp preservation

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