Amelioration of ketoconazole in lipid nanoparticles for enhanced antifungal activity and bioavailability through oral administration for management of fungal infections.

The objective of the investigation was the development and characterization of (KZ) loaded lipid nanoformulations (KZ-LNFs) such as solid lipid nanoparticles (KZ-SLNs) and nanostructured lipid carriers (KZ-NLCs) that could improve oral bioavailability and enhance antifungal activity through oral delivery. KZ-LNFs were prepared using homogenization aided with the sonication method, using dynasan 116 as solid lipid and castor oil as liquid lipid. Prepared KZ-LNFs were evaluated for physicochemical characteristics and optimized. Optimized KZ-LNFs were further evaluated using X-ray diffractometry (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), stability, and freeze-drying. Furthermore, optimized KZ-LNFs were evaluated for in vitro antifungal efficacy against Candida albicans, and bioavailability studies were carried out in Wistar rats by single oral administration compared with KZ suspension as control formulation (KZ-CS). The optimized KZ-SLN formulation showed particle size and entrapment efficiency of 210.9 ± 3.4 nm and 84.8 ± 1.5% compared to 167.8 ± 5.8 nm and 95.3 ± 2.0% for optimized KZ-NLC formulation. XRD complemented and confirmed DSC results, KZ was well entrapped inside the core of carrier systems in a molecularly dispersed state. Furthermore, KZ-LNFs formulations exhibited a spherical shape in SEM. In vitro release studies demonstrated a sustained release profile for KZ from KZ-LNFs over a 24 h. After oral...
Source: Chemistry and Physics of Lipids - Category: Lipidology Authors: Tags: Chem Phys Lipids Source Type: research