Genotoxicity and <i>in vitro</i> investigation of Gefitinib-loaded polycaprolactone fabricated nanoparticles for anticancer activity against NCI-H460 cell lines

For non-small cell lung cancer (NSCLC) treatment, a BCS class II drug, Gefitinib, was widely used. Due to poor bioavailability, uncontrollable drug release, Gefitinib witnessed side effects. To circumvent such associated problems, optimized encapsulated polycaprolactone (PCL) nanoparticles with three different molecular weights of PCL (average Mn?10,000, Mn?45,000 & Mn?80,000) were developed using Box–Behnken design while understanding the influence critical process parameters nanoparticles. morphological characterizations, SEM, TEM, AFM Hemocompatibility, platelet aggregation, and erythrocyte membrane integrity tests used test for biocompatibility; excellent biocompatibility reported during these tests. The in-vitro release studies confirmed that Gefitinib-PCL10,000NPs, Gefitinib-PCL45,000NPs, Gefitinib-PCL80,000 NPs, show significant initial burst effects, later possessed zero-order kinetics. genotoxicity assessed by cytokinesis-block micronucleus (CBMN) assay, indicating DNA damage in NCI-H460 micronuclei nuclear buds’ formation. Further, reactive oxygen species studies, MTT cytotoxicity assays at 24 48 h, stability, cellular uptake fluorescent PCL80,000NPs, apoptosis also carried out. As result, investigating stable Gefitinib-loaded poly-caprolactone could open up new research avenues, potentially lowering effects improving Gefitinib's profile treatment NSCLC.