Polymeric micelle gel with luliconazole: in vivo efficacy against cutaneous candidiasis in Wistar rats

Abstract

The objective of this research was focused on the design and development of luliconazole-loaded polymeric micelle hydrogel (LUL-PM-CHG) using quality by design (QbD) principle to improve the penetration and retention of LUL in the skin. The optimization of the formulation involved the utilization of a Box-Behnken design with three factors and three levels. The impact of specific formulation variables, namely the ratio of poloxamer P123 and F127, sonication time, and the quantity of drug, was investigated in terms of particle size, micellar incorporation efficiency, and polydispersity index. The LUL-loaded P123/F127 mixed micelles involved the thin film hydration method for thin preparation. The characteristics of optimized formulation include a particle size of 226 ± 8.52 nm, a polydispersity index (PDI) of 0.153 ± 0.002, a zeta potential (ZP) of 30.15 ± 2.32 mV, and a micellar incorporation efficiency (MIE) of 88.38 ± 3.84%. In vitro release studies indicated a sustained release of LUL-PM-CHG for a duration of up to 8 h. The MIC, GI₅₀, and GI₉₀ of different formulations on Candida albicans were determined using both the microtiter broth dilution method and the plate method and showed that LUL-PM-CHG exhibited the highest antifungal activity compared to the other formulations, with MIC values of 3.25 ± 0.19 ng/mL, GI₅₀ values of 37.11 ± 2.89, and GI₉₀ values of 94.98 ± 3.41 The study also measured the % of inhibition activity and the generation of intracellular reactive oxygen species (ROS) using flow cytometry. LUL-PM-CHG showed the highest percentage of inhibition (75.5%) and ROS production (MFI-140951), indicating its enhanced activity compared to LUL-CHG and LUL. Fungal infection was induced in Wistar rats using immunosuppressant’s treatment followed by exposure to C. albicans. Finally, in vivo fungal scaling and histopathological studies indicated a reduction in fungal infection in Wistar rat skin after treatment. The obtained results suggested that LUL-PM can serve as a promising formulation to enhance luliconazole antifungal activity and increase patient compliance.