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
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).