Chitosan Nano-encapsulation Enhances Gedunin Cytotoxicity A gainst Human Non-small-cell Lung Cancer (NCI-H292) Cell Line

Background: Poor pharmacokinetic profile, bioavailability, solubility and toxicity to healthy tissues hamper clinical application. Encapsulation of gedunin from the neem plant possessing anticancer potential, in chitosan nanoparticles, may overcome these issues and increase antiproliferative property. Methods: Chitosan nanoparticles were prepared by an ionic gelation method. Cells were exposed to gedunin (1.5625 - 50 μg/mL) and the nanoformulation (0.469 - 15 μg/mL) for 24, 48 and 72 h, with paclitaxel as the positive control. Their inhibitory activities were investigated by Sulphorhodamine B assay, coupled with microscopic visualization through a phase-contrast microscope. Results: Encapsulation efficiency of gedunin in chitosan was 98 %, with average particle size of 163.2 ± 24.28, and a zeta potential of +24.2 ± 3.75. Dose- and time-dependent cytomorphological changes resulting in cell death were observed. Nano-gedunin demonstrated much higher antiproliferative activities against NCI-H292 cells at significant levels (p < 0.05). The mean IC50 values for gedunin were approximately 26, 23, and 20 μg/mL at 24, 48, and 72 h, respectively. In contrast, chitosan- encapsulated gedunin recorded a 3 to 8-fold decrease (7.5, 5, and 2 μg/mL). Conclusion: The chitosan nano-delivery system enhanced the cytotoxic activity of gedunin in vitro against NCI-H292 cells and reduced cytotoxicity towards normal lung fibroblast cells (MRC-5).