Polymeric Nanoparticle‐Based Drug Delivery System for Targeted Lung Cancer Therapy

Abstract Gefitinib, a tyrosine kinase inhibitor, is clinically effective against non‐small cell lung cancer; however, its therapeutic potential is restricted by poor solubility, low oral bioavailability, and nonspecific tissue distribution. To address these limitations, dextran‐conjugated polycaprolactone (Dex‐b‐PCL) copolymeric nanoparticles were developed using a Quality by Design (QbD) approach. Copolymer synthesis was followed by optimization of formulation variables employing a 2³ full factorial design through Design Expert 13 software. The nanoparticles were fabricated via a modified nanoprecipitation technique, yielding a stable system with high drug encapsulation efficiency and desirable physicochemical characteristics. Evaluation demonstrated nanoscale size distribution, low polydispersity index, and negative surface charge, indicating colloidal stability. In vitro drug release studies revealed a sustained release pattern consistent with Fickian diffusion kinetics anddescribed by the Korsmeyer‐Peppas model. Cellular uptake investigations using A549 lung cancer cells showed time‐dependent internalization of fluorescently labeled nanoparticles, with enhanced intracellular retention over 72 h. The formulation exhibited a lower IC50 value (5.2399 µM) compared to free drug (6.299 µM), signifying improved cytotoxic efficacy. Stability assessments under ICH guidelines and sterility testing confirmed the suitability of the formulation for parenteral administration. These findings underscore the potential of Dex‐b‐PCL nanoparticles as an advanced nanocarrier system for gefitinib delivery.