Enhanced anticancer activity of naringenin-encapsulated poly (lactic acid)/neem gum nanoparticles for breast cancer cells

Naringenin (NGN) is a plant-derived flavonoid that has attracted significant interest due to its antioxidant and anticancer characteristics. However, its therapeutic applications are limited because of its low solubility in water, instability, and bioavailability at the target site. Therefore, the present study aimed to formulate NGN-encapsulated poly (lactic acid) (PLA)/neem gum (NEG) nanoparticles (NPs) to enhance their anticancer potency against breast cancer cells. The modified solvent evaporation-emulsification technique was followed to formulate NGN-PLA/NEG NPs, and their physicochemical properties, stability, drug release, and cytotoxic potentials were evaluated. The formulated NGN-PLA/NEG NPs showed a semi-crystalline nature, a zeta potential of +0.152 mV, a polydispersity index of 0.234, and a z-average particle size of 44.14 nm with spherical shape. NGN's encapsulation efficiency and loading capacity into PLA/NEG NPs were 77.72 ± 1.38% (w/w) and 8.57 ± 0.4% (w/w), respectively. At pH 5.8, NGN-PLA/NEG NPs released more NGN (78.46 ± 0.96%) than at pH 3.5 and 7.4. The MTT assay showed that NGN-PLA/NEG NPs had a significantly higher cytotoxic efficacy than free-NGN in Michigan Cancer Foundation 7 (MCF-7) cells, with an IC₅₀of 31.51 μg ml^-1. The IC₅₀concentration of NGN-PLA/NEG NPs significantly elevated the intracellular reactive oxygen species level, caspase-3 and -9 activity, and triggered apoptosis in MCF-7 cells. Apoptotic indicators, such as membrane blebbing and nuclear disintegration, have been observed in cancer cells treated with NGN-PLA/NEG NPs. These findings suggested that NGN-PLA/NEG NPs, which target NGN delivery into MCF-7 cells and promote endocytosis, could have potent anticancer activity against breast cancer cells.