Preparation of novel in situ film-forming gel impregnated with clotrimazole-loaded liquid crystalline nanoparticles: In vitro, ex vivo, in vivo dermatopharmacokinetic and antifungal evaluation.

In an attempt to conquer the significant concerns, viz. patient discomfort due to repeated application, low skin permeability, retention, and low therapeutic efficacy of conventional topical formulations (creams, ointments, etc.) for the management of fungal infection caused by Candida albicans, an alternative delivery system was aimed. Thus, the study was contemplated to formulate in situ film-forming gel impregnated with clotrimazole-loaded liquid crystalline nanoparticles (CLT-LCNP@FFG) for enhanced antifungal activity against Candida albicans infection. First, we optimized CLT-LCNP, which shows a nanosized particle (271.4 nm), encapsulation efficiency (90.00 %), drug loading (18.30 %), sustained drug release, and was found to be non-cytotoxic on HaCaT cell lines. CLT-LCNP@FFG formed a transparent, thin, homogeneous, and substantive film after topical application. Ex vivo skin permeation and skin deposition study demonstrated that CLT-LCNP@FFG showed 3-fold higher skin permeation and 207 % higher CLT deposition in skin layers than a marketed product (CLT-MKT; Canesten, 1% w/w CLT). The simulation analysis suggested CLT-LCNP@FFG maintained CLT concentration above the MIC for 3 times the days in rat skin and 5 times the days in human skin as compared to CLT-MKT, suggesting a reduction in dosing frequency. In vivo dermatopharmacokinetic parameters improved significantly with CLT-LCNP@FFG. The enhanced therapeutic efficacy of CLT-LCNP@FFG was confirmed by in vitro and in vivo antifungal activity experiments. These results showed that this hybrid system could potentially improve the efficacy of antifungal agents and patient compliance in the treatment of fungal infections.