1 research outputs found
Tenofovir Containing Thiolated Chitosan Core/Shell Nanofibers: <i>In Vitro</i> and <i>in Vivo</i> Evaluations
It is hypothesized
that thiolated chitosan (TCS) core/shell nanofibers
(NFs) can enhance the drug loading of tenofovir, a model low molecular
weight and highly water-soluble drug molecule, and improve its mucoadhesivity
and <i>in vivo</i> safety. To test this hypothesis, polyÂ(ethylene
oxide) (PEO) core with TCS and polylactic acid (PLA) shell NFs are
fabricated by a coaxial electrospinning technique. The morphology,
drug loading, drug release profiles, cytotoxicity and mucoadhesion
of the NFs are analyzed using scanning and transmission electron microscopies,
liquid chromatography, cytotoxicity assays on VK2/E6E7 and End1/E6E7
cell lines and <i>Lactobacilli crispatus</i>, fluorescence
imaging and periodic acid colorimetric method, respectively. <i>In vivo</i> 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, and PEO/TCS-PLA NFs are
118.56, 9.95, and 99.53 nm, respectively. The NFs exhibit smooth surface.
The drug loading (13%–25%, w/w) increased by 10-fold compared
to a nanoparticle formulation due to the application of the electrospinning
technique. The NFs are noncytotoxic at the concentration of 1 mg/mL.
The PEO/TCS-PLA core/shell NFs mostly exhibit a release kinetic following
Weibull model (<i>r</i><sup>2</sup> = 0.9914), indicating
the drug release from a matrix system. The core/shell NFs are 40–60-fold
more bioadhesive than the pure PEO based NFs. The NFs are nontoxic
and noninflammatory <i>in vivo</i> 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