Formulation development and characterization of luliconazole loaded−mesoporous silica nanoparticles (MCM−48) as topical hydrogel for the treatment of cutaneous candidiasis

Abstract

The conventional formulation of luliconazole (LCZ) faces challenges such as poor solubility and limited skin retention upon application. Therefore, the focus of this research was to develop and characterize mesoporous silica nanoparticles (MSN) that can effectively deliver luliconazole for the treatment of cutaneous candidiasis fungal infection.The MSNs were optimized by central composite design and synthesized using the sol−gel method. Factors such as stirring time and surfactant ratio were varied to investigate their impact on particle size and Polydispersity index (PDI). Subsequently, the MSN surface was functionalized with both amine (positively charged) and phosphonate groups (negatively charged) using 3-aminopropyltriethoxysilane (APTES) and 3trihydroxysilyl propyl methylphosphonate (THMP).The efficacy of the optimized luliconazole−loaded MSNs was evaluated through various comparative studies, including in-vitro and in-vivo antifungal assessments, ex-vivo permeation and skin retention experiments, acute dermal irritation tests, and histopathological analysis. These evaluations were compared with the pure drug and a commercially available formulation.The optimized MSNs exhibited high porosity and spherical particle sizes ranging from 300 to 400 nm. They demonstrated excellent physical and chemical stability, indicating compatibility between the drug and the MSN structure. The successful loading of luliconazole into the nanopores of the MSNs was confirmed through Brunauer Emmett Teller (BET) analysis.The luliconazole−loaded MSN (LCZ−MSN) gel exhibited a controlled release profile, sustaining drug release for up to 24 h. The solubility of the drug was 12 times higher compared to the free form, and the MSNs enhanced skin retention by six−fold compared to the pure drug. In an in-vivo cutaneous candidiasis rat model, the enhanced efficacy of the MSNs was evident, highlighting the potential of this innovative approach for controlled release and solubility enhancement of poorly soluble drugs, with no observed skin irritation.Overall, this research showcases the potential of mesoporous silica nanoparticles as a promising approach for controlled delivery and improved solubility of poorly soluble drugs like luliconazole, thereby addressing the challenges associated with conventional formulations and offering a novel strategy for treating cutaneous candidiasis fungal infection.