Smart Antifungal Therapy: Lipase-Responsive Ketoconazole and Atorvastatin Co-loaded Poly є-caprolactone Nanoparticles for Cutaneous Candidiasis.

This study aimed to fabricate lipase-sensitive, polymeric nanoparticles (PNPs) in the film forming spray for co-delivering Ketoconazole (KTZ), and Atorvastatin (ATV), against cutaneous candidiasis. Poly (є-caprolactone) was utilized to synthesize (PNPs) through the Nanoprecipitation technique. The Co-loaded KTZ-ATV PNPs were optimized by Design Expert for particle size (PS), zeta potential (ZP), and polydispersity index (PDI). The optimized KTZ-ATV Co-loaded PNPs were extensively characterized by FTIR, XRD, DSC, and TEM. KTZ-ATV Co-loaded PNPs were loaded in the film forming spray (FFS). In vitro release, skin permeation, deposition, and irritation studies were conducted. In vitro and in vivo antifungal efficacy of Co-loaded PNPs based FFS was analyzed. The optimized formulation exhibited PS of 261 ± 0.8 nm, ZP potential of -23 mV ± 1.0, PDI of 0.112 ± 0.01, and %Entrapment Efficiency of 86.7 ± 2.11 for KTZ and 85 ± 1.61 for ATV. In vitro release studies of KTZ-ATV PNPs exhibited a sustained and lipase responsive drug release at skin pH(5.5). Skin deposition and permeation studies of Co-loaded PNPs based FFS .demonstrated significantly enhanced skin permeation and deposition in comparison to marketed cream and exhibited no observable irritation risk. In vitro antifungal assay exhibited a profoundly increased zone of inhibition (ZOI) in comparison to the marketed formulations. Co-loaded PNPs based FFS exhibited substantially increased antifungal potential in in vivo cutaneous candidiasis model. The findings suggest that Co-loaded PNPs based FFS could serve as a more promising therapeutic option for treating cutaneous candidiasis, offering an exceptional antifungal potential, targeted activity, enhanced skin deposition, and improved permeation.