Frovatriptan Succinate Loaded Lipid Nanoparticles: Formulation, Evaluation, Stability Study and Shelf Life Determination

Aims: The aim of the research work was to prepare and optimize the Frovatriptan Succinate (FVN) loaded solid lipid nanoparticles. Methods: SLNs were developed by solvent emulsification diffusion technique and evaluated for particle size, PDI, zeta potential, in-vitro drug release, and finally stability study was conducted for the detection of shelf life. Results: The optimized formulation exhibited particle size, PDI, and zeta potential 122.85±9.24 nm, 0.129 and -25.85 mV, respectively. In-vitro drug release study exhibited biphasic drug release pattern. Initially (in first two hrs) the drug was release in fast manor i.e. burst release (32.36±7.28 %). It might be due to the presence of drug on the surface of SLNs. After 2 hrs of study, the release pattern became sustained up to 24 hrs. The total amount of drug release in 24 h was found to be 91.29 ± 8.26%. Various kinetic models were applied to evaluate the release pattern of the drug form the formulation. Higuchi model was found to be the best fitted with the R2 value of 0.9482. The release mechanism was found to be the Fickian type with the release exponent (n) value of 0.4386. Finally, stability study was conducted. The formulation was found to be the stable under the studied conditions. The shelf life of the formulation was found to be 1.77 years. Conclusion: Finally, it could be concluded that, the SLNs are the suitable carrier for the delivery of FVN .

Design and Evaluation of Acyclovir Niosomes

The current study aims to formulate and evaluate acyclovir loaded niosomes for sustained release of acyclovir. Stable Acyclovir loaded Niosomes can be prepared by hand shaking method and ether injection method with Span 80 and cholesterol in the ratio of 1:1, 2:1, and 3:1. Preformulation studies and drug excipients compatibility studies was done initially and results directed the further course of formulation. Most of the vesicles are spherical in shape, the size range of the vesicles, fall in the narrow size range of 0.5-5 and 0.5-2.5 by hand shaking method and ether injection method respectively. A high % of Acyclovir can be encapsulated in the vesicles (75-84%) prepared by hand shaking method. Concentration of non-ionic surfactant such as Span 80 might influences the drug release pattern of all formulation. In vitro release of Acyclovir from niosomes was very slow when compared to the release from pure Acyclovir solution. Drug release studies showed that the niosomal preparation was stable at refrigeration temperature (40C). The vesicles prepared by hand shaking method were found to be larger in size as compared to vesicles prepared by ether injection method. Almost constant drug release was observed in all formulations indicating zero order release pattern.

Developing a Glyoxal-Crosslinked Chitosan/Gelatin Hydrogel for Sustained Release of Human Platelet Lysate to Promote Tissue Regeneration

The clinical application of human platelet lysate (HPL) holds promise for tissue regeneration, and the development of an efficient vehicle for its delivery is desired. Chitosan-based hydrogels are potential candidates, but they often exhibit weak mechanical properties. In this study, a chitosan/gelatin (CS-GE) hydrogel crosslinked by glyoxal was fabricated for sustained release of HPL. The influence of HPL on Hs68 fibroblast and human umbilical vein endothelial cell (HUVEC) culture was evaluated, and we found that supplementing 5% HPL in the medium could significantly improve cell proliferation relative to supplementing 10% fetal bovine serum (FBS). Moreover, HPL accelerated the in vitro wound closure of Hs68 cells and facilitated the tube formation of HUVECs. Subsequently, we fabricated CS-GE hydrogels crosslinked with different concentrations of glyoxal, and the release pattern of FITC-dextrans (4, 40 and 500 kDa) from the hydrogels was assessed. After an ideal glyoxal concentration was determined, we further characterized the crosslinked CS-GE hydrogels encapsulated with different amounts of HPL. The HPL-incorporated hydrogel was shown to significantly promote the proliferation of Hs68 cells and the migration of HUVECs. Moreover, the release pattern of transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor-BB (PDGF-BB) from hydrogel was examined in vitro, demonstrating a sustained release profile of the growth factors. Finally, the chick chorioallantoic membrane assay revealed that HPL encapsulation in the hydrogel significantly stimulated angiogenesis in ovo. These results demonstrate the great potential of the crosslinked CS-GE hydrogel to serve as an effective delivery system for HPL to promote tissue regeneration.

Effect of different phosphorus sources applied with phosphate solubilizing bacteria on bio-geochemical properties and phosphorus release pattern in vertisol

Various phosphorus (P) fertilizers are used for crop production in different types of soil. But there is a knowledge gap in choosing the right source and form of P fertilizers to enhance the applied fertilizer use efficiency. An experiment was taken to identify the best phosphorus source and its effectiveness as a source of P in vertisol to unravel this problem of selecting suitable P fertilizer. With this background, an incubation experiment was conducted under laboratory condition to determine the phosphorus release pattern of different P sources [Single Super Phosphate (SSP), Rock Phosphate (RP), Diammonium Phosphate (DAP), Nano phosphate (Nano P), Phosphocompost (PC)] applied with phosphate solubilizing bacteria (PSB) and their influence on biogeochemical properties in vertisol. Experimental results emphasized that P release from different sources was influenced by soil pH, electrical conductivity (EC), cation exchange capacity (CEC), soil organic carbon (SOC), and microbial population. Applied P sources significantly(p=0.05) influenced the CEC, SOC, and microbial population except for soil pH and Ec. The maximum release in available P was obtained at 30 and 60 days after incubation with SSP +PSB (35.8 and 40.1 mg kg-1) and Nano P + PSB (33.9 and 38.6 mg kg-1) applied treatments, respectively.Whereas at 90 days after incubation Nano P + PSB (42.3 mg kg-1) and Phosphocompost + PSB (40.4 mg kg-1) treatments recorded the maximum P availability and minimum P (15.2, 13.9 and 11.8 mg kg -1) release was noticed in the control treatment throughout the period of incubation. It was evident that SSP or Nano P along with PSB application might be the best P source for Vertisol.

Polyvinyl Alcohol/Chitosan Single-Layered and Polyvinyl Alcohol/Chitosan/Eudragit RL100 Multi-layered Electrospun Nanofibers as an Ocular Matrix for the Controlled Release of Ofloxacin: an In Vitro and In Vivo Evaluation

A novel nanofiber insert was prepared with a modified electrospinning method to enhance the ocular residence time of ofloxacin (OFX) and to provide a sustained release pattern by covering hydrophilic polymers, chitosan/polyvinyl alcohol (CS/PVA) nanofibers, with a hydrophobic polymer, Eudragit RL100 in layers, and by glutaraldehyde (GA) cross-linking of CS-PVA nanofibers for the treatment of infectious conjunctivitis. The morphology of the prepared nanofibers was studied using scanning electron microscopy (SEM). The average fiber diameter was found to be 123 ± 23 nm for the single electrospun nanofiber with no cross-linking (OFX-O). The single nanofibers, cross-linked for 10 h with GA (OFX-OG), had an average fiber diameter of 159 ± 30 nm. The amount of OFX released from the nanofibers was measured in vitro and in vivo using UV spectroscopy and microbial assay methods against Staphylococcus aureus, respectively. The antimicrobial efficiency of OFX formulated in cross-linked and non-cross-linked nanofibers was affirmed by observing the inhibition zones of Staphylococcus aureus and Escherichia coli. In vivo studies using the OFX nanofibrous inserts on a rabbit eye confirmed a sustained release pattern for up to 96 h. It was found that the cross-linking of the nanofibers by GA vapor could reduce the burst release of OFX from OFX-loaded CS/PVA in one layer and multi-layered nanofibers. In vivo results showed that the AUC0–96 for the nanofibers was 9–20-folds higher compared to the OFX solution. This study thus demonstrates the potential of the nanofiber technology is being utilized to sustained drug release in ocular drug delivery systems.

Hypo-osmotic Stress Induces ATP Release via Volume-regulated Anion Channels in Undifferentiated Mammary Cells

The high interstitial ATP concentration in the cancer microenvironment is a major source of adenosine, which acts as a strong immune suppressor. However, the source of ATP release has not been elucidated. We measured the ATP release during hypotonic stress using a real-time ATP luminescence imaging system in primary cultured mammary cells and in breast cell lines. In primary cultured cells, ATP was intermittently released with transient-sharp peaks, while in breast cell lines ATP was released with a slowly rising diffuse pattern. The diffuse ATP release pattern was changed to a transient-sharp pattern by cholera toxin treatment and the reverse change was induced by transforming growth factor (TGF) β treatment. DCPIB, an inhibitor of volume-regulated anion channels (VRACs), only suppressed the diffuse pattern. The inflammatory mediator sphingosine-1-phosphate (S1P) induced a diffuse ATP release pattern isovolumetrically. The knockdown of A isoform of leucine-rich repeat-containing protein 8 (LRRC8A), the essential molecular entity of VRACs, using shRNA suppressed the diffuse pattern. These results suggest that abundantly expressed VRACs are a conduit of ATP release in undifferentiated cells, including cancer cells.