Development and In-Vitro Evaluation of Eugenol-Based Nanostructured Lipid Carriers for Effectual Topical Treatment Against C. albicans.

ABSTRACT

The main objective of the experiment is to develop and evaluate hydrogel-bearing nanostructured lipid carriers (NLCs) loaded with ketoconazole (KTZ) for the effective treatment of candidiasis. The eugenol was used as a liquid lipid (excipient) for the development of KTZ-loaded NLCs and was explored for anti-fungal effect. The production of NLCs involves high energy processes to generate spherical, uniform particles, having a higher percentage of entrapment efficiency (%EE) for KTZ with 89.83 ± 2.31 %. The data from differential scanning calorimeter (DSC), powder x-ray diffraction (PXRD), and attenuated total reflectance (ATR) demonstrated the KTZ dispersion in NLCs. The NLCs loaded hydrogel possessed optimum spreadability and exhibited shear thinning behavior, indicating the ease of application of the final formulation. The 6.41-fold higher transdermal flux (Jss) was governed for KTZ from KTZ-NLC than coarse-KTZ, which explains the usefulness of NLCs. The KTZ-NLCs exhibited significant 2.58 and 6.35-fold higher retention in the stratum corneum and viable epidermis of the skin. The cell cytotoxicity studies using human dermal fibroblast cell (HDFS) lines depicted the usefulness of NLCs in reducing cell toxicities for KTZ. The KTZ-NLCs were found to inhibit planktonic growth and hyphal transition and showed a larger zone of inhibition against C. albicans strains with a MIC-50 value of 0.39 µg/mL. The antibiofilm activity of KTZ-NLCs at lower concentrations, in contrast to plain KTZ, explained the interaction of developed NLCs with fungal membranes. The overall results depicted the effectiveness of the loading KTZ in the lipid matrix to achieve antifungal activity against C. albicans.