Pimozide-loaded nanostructured lipid carriers: Repurposing strategy against lung cancer

Abstract

Objective: This study aimed to repurpose pimozide (PMZ) by incorporating it into nanostructured lipid carriers (NLC) using a modified melting emulsion ultrasonication method. Methods: We employed stearic and oleic acids in a 1:1 ratio as lipids, with Tween 80 and PEG 4000 as surfactants. The formulation was analyzed for particle size, zeta potential, and encapsulation efficiency. Transmission electron microscopy (TEM) was used to confirm the spherical shape of the particles. The release profile of PMZ-NLC was evaluated under different pH conditions, and anticancer activity was tested on A549 cell lines. Results: The PMZ-NLC exhibited an average particle size of 136 ± 2.9 nm, a zeta potential of −25.1 ± 0.9 mV, and an encapsulation efficiency of 86% ± 11. TEM confirmed the spherical shape of the NLCs. PMZ release from PMZ-NLC was pH-sensitive, enhancing tumor targeting. IC50 values were 16.5 μM for free PMZ and 12.9 μM for PMZ-NLC after 72 h. Discussion: PMZ-NLC demonstrated improved anticancer activity compared to free PMZ, suggesting that encapsulation enhances the drug's effectiveness. The pH-sensitive release profile supports its potential for targeted therapy in lung cancer. Conclusions: PMZ-NLC showed potential as a safe and effective strategy for lung cancer treatment. Further investigation is warranted to evaluate its in vivo efficacy, long-term safety, and clinical application.