Formulation of pullulan-assisted nanoparticles for improved dasatinib cytotoxicity in A549 lung carcinoma cells

Dasatinib (DAS) exhibits therapeutic potential for the treatment of lung cancer. However, its clinical utility is marred owing to poor solubility, low oral bioavailability, and rapid systemic clearance. Therefore, the current investigation is aimed to develop and optimize a polymeric nanoparticulate delivery system for DAS to increase its physicochemical properties and anticancer potential. Herein, pullulan was used as a stabilizer and encapsulating agent because of its biocompatibility and structural flexibility, allowing for effective DAS entrapment and controlled release. DAS-loaded nanoparticles were optimized employing a Box-Behnken design. The formulation was characterized for particle size, entrapment efficiency (% EE), zeta potential, in vitro drug release, and cytotoxicity against A549 lung cancer cells. The optimized formulation exhibited the particle size of 135.3 nm, EE of 92.8 %, and a zeta potential of -7.9 mV. FTIR and DSC analyses confirmed no significant drug-excipient incompatibility and corroborated successful drug encapsulation. The in vitro release studies demonstrated sustained release of DAS over 48 h at pH 7.4 (71.84 ± 3.12 %) and 6.8 (84.65 ± 4.10 %). DAS-loaded nanoparticles exhibited significantly higher cytotoxicity (65.49 %) compared to plain DAS (42.23 %). Overall, a pullulan-based nanoparticulate system offers a promising technique for improving DAS delivery and therapeutic efficacy in lung cancer treatment.