Formulation development and evaluation of antifungal agents using lipidic nanocarriers for improved biopharmaceutical attributes

Abstract

Fungal infections are difficult to treat as most fungal cells have specialized efflux system resulting in frequent drug resistance. Sub-optimal concentration of antifungal agents at the site of infection, poor compliance to therapy, poor delivery modalities, and active antifungal efflux are responsible for frequent recurrence, chronic fungal infections and most seriously drug resistance. Systematically optimized (using CCD) KTZ-SLN formulation which is extensively characterized. This is the first time when 2% KTZ concentration was loaded into SLNs. The investigation is supported by several proof-of-concept studies which were designed to confirm its capacity to permeate stratum corneum and reach lower skin layers such as transdermal flux, retention of KTZ in rat skin. Significantly higher Cmax values were also observed from KTZ-SLNs observed in rat skin tissue. AmB-SLNs for intravenous administration using hot high pressure homogenization technique coupled with Box-Behnked design enabled optimization of its composition. AmB-SLNs revealed no toxic effects when interacted with cell lines and RBCs while free AmB was highly toxic. Single-dose i.v. pharmacokinetic studies in rat plasma showed higher AUMC0-and#8734;). Acute and sub acute toxicity studies indicated no mortality. newline