Chitosan functionalized PCL Nanoparticles Bearing Tyrosine Kinase Inhibitor Osimertinib Mesylate for Effective Lung Cancer Therapy.

Lung cancer ranks second position among the cancer-related deaths. Osimertinib mesylate (OSM) is a tyrosine-kinase-inhibitor which can effectively treat NSCLC, but still there are certain limitations and side effects which could be circumvented by polymeric nanoparticles approach. Hence, this research was aimed to develop drug-loaded biodegradable poly caprolactone nanoparticles (PCL-NPs) such as OSM-loaded PCL-NPs (PCL-OSM-NPs) and chitosan fabricated OSM-loaded PCL-NPs (CS-PCL-OSM-NPs) to achieve active-targeting of OSM in the cancerous lung tissue. Thus CS-PCL-OSM-NPs enhances the anticancer efficacy due to active targeting nature and thereby reduces off-target side effects of OSM in the NSCLC treatment.Blank PCL-NPs, PCL-OSM-NPs, and CS-PCL-OSM-NPs were prepared by nanoprecipitation method. Optimized blank PCL-NPs, PCL-OSM-NPs, and CS-PCL-OSM-NPs exhibited the mean particle size of 90.2 ± 4.7nm, 167.7 ± 2.9nm, and 233.7 ± 4.8nm respectively. The %EE of PCL-OSM-NPs was found to be 68.4 ± 3.2%. In-vitro drug release study demonstrated sustained release profile of 69.5 ± 5% and 65.7 ± 1.5% for OSM from both the PCL-OSM-NPs and CS-PCL-OSM-NPs respectively. The PCL-OSM-NPs and CS-PCL-OSM-NPs demonstrated the inhibition of 82.2 ± 0.5% and 81.9 ± 0.2% in A549 cancer cells respectively which clearly signified the improved efficacy. Moreover, the PCL-OSM-NPs and CS-PCL-OSM-NPs exhibited significantly less haemolysis than OSM indicating safety of the formulation.These findings indicate that biohaemocompatibe CS-PCL-OSM-NPs is an attractive option to treat NSCLC with enhanced anticancer activity and reduced side effects.