It is hypothesized that a thiolated chitosan (TCS) core/shell nanofiber (NF) can enhance the drug loading of tenofovir, a model low molecular weight and highly water soluble drug molecule, improve its mucoadhesivity, and in vivo safety. To test this hypothesis, PEO core with TCS shell NFs are fabricated by a coaxial electrospinning technique. The morphology, drug loading, drug release profiles, cytotoxicity and mucoadhesion of the NFs are analysised using scanning and transmission electron microscopies, liquid chromatography, cytotoxicity assays on VK2/E6E7 and End1/E6E7 cell lines and Lactobacilli crispatus, and periodic acid colorimetric method, respectively. In vivo safety studies are performed in C57BL/6 mice followed by H&E and immunohistochemical (CD45) staining analysis of genital tract. The mean diameters of PEO, PEO/TCS, PEO/TCS-PLA NFs are 118.56, 9.95, and 99.53 nm. The NFs exhibit smooth surface with average diameters. The drug loading (13%-25%, w/w) increased by 10 folds compared to a nanoparticle formulation due to the investigation of the electrospinning technique. The NFs are non-cytotoxic at the concentration of 1 mg/ml. The PEO/TCS-PLA core/shell NFs mostly exhibit a release kinetic following Weibull model (r=0.9914), indicating the drug release from a matrix system.The core/shell NFs are 40-60 fold more bioadhesive than the NFs of PEO only. The NFs are non-toxic and non-inflammatory in vivo after daily treatment for up to 7 days. Owing to their enhanced drug loading and preliminary safety profile, the TCS core/shell NFs are promising candidates for the topical delivery of HIV/AIDS microbicides such as tenofovir.
Tenofovir containing thiolated chitosan core/shell nanofibers: in vitro and in vivo evaluations.