betadex and Hepatitis-C

The present work-study the improvement of the loading and release efficiency of sofosbuvir drug (SOF) for anti-hepatitis C virus (HCV) by the combination process with β-cyclodextrin (βCD) basket to form a novel self-assembly βCD-SOF which load on the chitosan nanoparticle (Cs NPs) to form a novel hybrid composite (Cs@βCD-SOF). The characterization process performs for confirming the formation of hybrid composite with various methods. The loading efficiency of SOF is performed by UV-Vis spectroscopy, which is reported at 94.54% for Cs@βCD-SOF, while in the reverse case the efficiency is βCD-SOF@Cs 65.2%. The binding constant (K

Topics: Animals; Antiviral Agents; beta-Cyclodextrins; Chitosan; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C; Mice; Nanoparticles; Pharmaceutical Preparations; Sofosbuvir; Treatment Outcome

In this study, we establish that cholesterol and sphingolipid associated with hepatitis C virus (HCV) particles are important for virion maturation and infectivity. In a recently developed culture system enabling study of the complete life cycle of HCV, mature virions were enriched with cholesterol as assessed by the molar ratio of cholesterol to phospholipid in virion and cell membranes. Depletion of cholesterol from the virus or hydrolysis of virion-associated sphingomyelin almost completely abolished HCV infectivity. Supplementation of cholesterol-depleted virus with exogenous cholesterol enhanced infectivity to a level equivalent to that of the untreated control. Cholesterol-depleted or sphingomyelin-hydrolyzed virus had markedly defective internalization, but no influence on cell attachment was observed. Significant portions of HCV structural proteins partitioned into cellular detergent-resistant, lipid-raft-like membranes. Combined with the observation that inhibitors of the sphingolipid biosynthetic pathway block virion production, but not RNA accumulation, in a JFH-1 isolate, our findings suggest that alteration of the lipid composition of HCV particles might be a useful approach in the design of anti-HCV therapy.

Topics: beta-Cyclodextrins; Carcinoma, Hepatocellular; Cell Line; Cell Line, Tumor; Cholesterol; Hepatitis C; Humans; Kidney; Liver Neoplasms; Membrane Microdomains; Plasmids; Sphingolipids; Sphingomyelin Phosphodiesterase; Virion

The purpose of this study was to develop and evaluate a solid nonaqueous oral dosage form for a new hepatitis C drug, PG301029, which is insoluble and unstable in water. Hydroxypropyl-beta-cyclodextrin (HPbetaCD) and PG301029 were dissolved in glacial acetic acid. The acetic acid was removed by rotoevaporation such that the drug exists primarily in the complexed form. The stability of formulated PG301029 was determined upon dry storage and after reconstitution in simulated intestinal fluid (SIF), simulated gastric fluid (SGF), and water. Formulated PG301029 was found to be stable upon storage and can be reconstituted with water to a concentration 200 times that of the intrinsic solubility. Once reconstituted, the powder dissolves rapidly and PG301029 remains stable for 21 hours in SGF, SIF, and water. The unique use of acetic acid and HPbetaCD results in a solid dosage form of PG301029 that is both soluble and stable in water.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Acetic Acid; Antiviral Agents; beta-Cyclodextrins; Calorimetry, Differential Scanning; Chromatography, High Pressure Liquid; Drug Stability; Hepatitis C; Solubility; Thiadiazoles