Enhanced anticancer activity of piperine: Structural optimization and chitosan-based microgels with boosted drug delivery

As a plant-derived drug, piperine possesses therapeutic efficacy for many diseases, but its inherent low solubility and bioavailability have greatly limited its clinical use. Herein, we extracted piperine from black pepper, opti-mized the structure of piperine to prepare various derivatives, and then explored the anticancer activity of these derivatives. Piperine and its derivatives have high anticancer selectivity against 4T1 cells, exhibiting obvious anticancer properties even at a low concentration of 100 mu g/mL. Furthermore, the physicochemical properties of piperine and its derivatives were investigated using density functional theory, demonstrating their considerable biological activity. Moreover, the chitosan-based microgels were prepared to encapsulate the hydrophobic piperine derivative with a high loading efficiency of 81.7 % to overcome the low water solubility of the piperine derivative. It is worth noting that excessive glutathione in tumor cells triggers the degradation of microgels and realizes controllable drug release of up to 72.3 %. Due to its excellent properties, chitosan-based microgels loaded with the piperine derivative can obtain good anticancer behavior of approximately 13.14 % cell viability against 4T1 cells. Therefore, the chitosan-based microgels overcome the low water solubility of the piperine derivative through encapsulation and thus further augment their delivery efficiency and cell internalization capability to realize excellent anticancer activity. This work demonstrates the enhanced anticancer efficacy of the hydrophobic plant-derived drug by means of structural optimization of piperine and chitosan-based microgels with boosted drug delivery.