Formulation optimization of chitosan surface coated solid lipid nanoparticles of griseofulvin: A Box-Behnken design and in vivo pharmacokinetic study

Abstract

Solid lipid nanoparticles (SLNs) are becoming increasingly favored for their robust biocompatibility and their capacity to enhance drug solubility, particularly for drugs with limited water solubility. This study delves into the effectiveness of the hot melt sonication technique in fabricating SLNs with high drug loading capabilities and sustained release characteristics. Griseofulvin (GF), chosen as a representative drug due to its poor water solubility, was encapsulated into SLNs composed of stearic acid. Optimization of chitosan-coated GF-loaded SLNs (CS-GF-SLN) was conducted using a Box-Behnken design. Utilizing the desirability approach, optimal parameters were determined, including a lipid quantity of 450.593 mg, chitosan content of 268.67 mg, and sonication duration of 2.14 h. These parameters resulted in a zeta potential of -34.8 mV and a particle size (PS) of 56.87 nm. Following optimization, the refined formulation underwent comprehensive assessment across various parameters. Notably, the drug encapsulated within SLNs exhibited sustained release over three days, as illustrated by the in-vitro drug release profile. The optimized formulation demonstrated a bioavailability enhancement by approximately 1.7 to 2.0 times compared to the conventional formulation. Furthermore, administration of drug-loaded SLNs to a macrophage cell line demonstrated no cytotoxicity, affirming their suitability as conventional drug delivery platforms for GF.