Enhanced Oral Bioavailability and Biodistribution of Voriconazole through Zein-Pectin-Hyaluronic Acid Nanoparticles

Nanotechnology-based drug delivery systems offer a solution to the pharmacokinetic limitations of voriconazole (VRC), including saturable metabolism and low oral bioavailability. This study developed zein/pectin/hyaluronic acid nanoparticles (ZPHA-VRC NPs) to improve VRC's pharmacokinetics and biodistribution. The nanoparticles had a spherical morphology with an average diameter of 268 nm, a zeta potential of −48.7 mV, and an encapsulation efficiency of 88%. Stability studies confirmed resistance to pH variations and digestive enzymes in simulated gastric and intestinal fluids. The in vitro release profile showed a controlled release, with 8% of the VRC released in 2 h and 16% over 24 h. Pharmacokinetic studies in rats demonstrated a 2.8-fold increase in the maximum plasma concentration and a 3-fold improvement in bioavailability compared to free VRC. Biodistribution analysis revealed enhanced VRC accumulation in key organs. These results suggest that ZPHA-VRC NPs effectively improve VRC's therapeutic potential for oral administration.