Poly-lactide-co-glycolide nanoparticles containing voriconazole for pulmonary delivery: in vitro and in vivo study

Poly-lactide-co-glycolide nanoparticles (207-605 nm) containing voriconazole (VNPs) were developed using a multiple-emulsification technique and were also made porous during preparation in presence of an effervescent mixture for improved pulmonary delivery. Pulmonary deposition of the particles was studied using a customized inhalation chamber. VNPs had a maximum of 30% (w/w) drug loading and a zeta potential (ZP) value around -20 mV. In the initial 2 hours, 20% of the drug was released from VNPs, followed by sustained release for 15 days. Porous particles had a lower mass median aerodynamic diameter (MMAD) than nonporous particles. Porous particles produced the highest initial drug deposition (similar to 120 mu g/g of tissue). The drug was detectable in lungs until 7 days and 5 days after administration, for porous and nonporous particles, respectively. VNPs with improved drug loading were successfully delivered to murine lungs. Porous nanoparticles with lower MMADs showed better pulmonary deposition and sustained presence in lungs.