In vitro appraisals and ex vivo permeation prospect of chitosan nanoparticles designed for schizophrenia to intensify nasal delivery

Abstract

The current study manifests the successful optimization and delivery of chitosan nanoparticles utilizing nasal route to overcome inherent issues of lurasidone hydrochloride (an antipsychotic drug) to curtail its bioavailability problems. Chitosan nanoparticles (CH-NPs) were prepared by ionic gelation technique and optimized using Box–Behnken design (BBD). In vitro drug release kinetics and ex vivo nasal permeation potential were determined. Chitosan NPs exhibited mean particle size (154.8 ± 4.5 nm), mean polydispersity index 0.433 ± 34.5; % EE 88.5 ± 0.05, and % DLC 8.8 ± 0.07. Transmission electron microscopy examinations revealed spherical particle size with uniform drug distribution. Physicochemical stability of CH-NPs was evaluated for 12 weeks, and they showed good stability at (25 ± 2 °C/60 ± 5% RH). In vitro release studies established supremacy of LH-CH-NPs compared to drug suspension (LH-DS) with cumulative drug release of 89.93% in pH 6.4 and 87.16 ± 3.78% in pH 7.4. Ex vivo nasal permeation studies revealed a 5.26-fold increment in nasal permeation by LH-NPs, and the cumulative amount of drug permeated through nasal mucosa from LH-CH-NPs was 2.58 ± 0.13 µg/cm2 × 10–2 compared to 1.02 ± 0.091 µg/cm2 × 10–2 from (LH-DS). Thus, in vitro and ex vivo results from LH-CH-NPs showed remarkable potential in improving solubilization fate and nasal permeation of LH, thereby leading to prospective in vivo fate in enhancing brain delivery of LH.