Optimization of Lurasidone HCl-Loaded PLGA Nanoparticles for Intramuscular Delivery: Enhanced Bioavailability, Reduced Dosing Frequency, Pharmacokinetics, and Therapeutic Outcomes.

Abstract

This study aimed to develop a nanoparticle drug delivery system using poly (lactic-co-glycolic acid) (PLGA) for enhancing the therapeutic efficacy of lurasidone hydrochloride (LH) in treatment of schizophrenia through intramuscular injection. LH-loaded PLGA nanoparticles (LH-PNPs) were prepared using the nanoprecipitation technique and their physicochemical characteristics were assessed. Particle size (PS), zeta potential, morphology, % encapsulation efficiency, % drug loading, drug content, and solid-state properties were analyzed. Stability, in vitro release, and in vivo pharmacokinetic studies were conducted to evaluate the therapeutic efficacy of the developed LH-PNPs. The optimized batch of LH-PNPs exhibited a narrow and uniform PS distribution before and after lyophilization, with sizes of 112.7 ± 1.8 nm and 115.0 ± 1.3 nm, respectively, and a low polydispersity index. The PNPs showed high drug entrapment efficiency, drug loading, and drug content uniformity. Solid-state characterization indicated good stability and compatibility, with a nonamorphous state. The drug release profile demonstrated sustained release behavior. Intramuscular administration of LH-PNPs in rats resulted in a significantly prolonged mean residence time compared with the drug suspension. These findings highlight that intramuscular delivery of the LH-PNP formulation is a promising approach for enhancing the therapeutic efficacy of LH in treatment of schizophrenia.