Enhanced therapeutic approach for vaginal candidiasis: chitosan nanoparticulate thermoreversible in situ gels for sustained clotrimazole delivery.

Abstract

This study aimed to develop and evaluate clotrimazole (CLZ)-loaded chitosan (CS) nanoparticles in a thermoreversible in situ gel for treating vaginal candidiasis (VC). Chitosan nanoparticles (CS-NPs) were prepared using ionotropic gelation with optimization through the design of experiments (DoE), considering factors such as chitosan pH, sodium tripolyphosphate (TPP) pH, the ratio of chitosan to TPP, and drug. Under optimal conditions (pH of CS, TPP, CS: TPP, and drug at 2, 2, 4:1, and 10 mg), nanoparticles exhibited desirable properties: particle size of 101.7 nm, polydispersity index (PDI) of 0.108, zeta potential of 35.4, and encapsulation efficiency of 98.36%. Thermoreversible in situ gels incorporating poloxamer (PXM) 407 and 188 were produced via the cold method and evaluated for mechanical and physicodynamic properties. It was found that nanoparticulate thermoreversible gel (NTG) prepared with 24% PXM 407, 4% PXM 188, 0.5% HPMC E-50, or 0.5% chitosan is suitable for vaginal administration, since it fulfills the in situ gel characteristics such as pH (4.7), gelation temperature and time (36 ℃ ± 0.2 and 4 ± 0.2 min), and viscosity (2690 cP (centipoise) at 25 ℃ and 15,600 cP at 37 ℃). In vitro release studies for the developed formulation showed 98% drug release over 72 h, with an extended residence time compared to the marketed formulation. In vitro antifungal and cytocompatibility studies revealed that the developed NTG was effective against VC and free from cytotoxicity.