Enhancing the therapeutic efficacy of piperine in colorectal cancer: development and evaluation of piperine-loaded PLGA-b-PEG copolymer nanoparticles

Abstract

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related morbidity and mortality worldwide. Piperine, a natural alkaloid from Piper nigrum L. and Piper longum L., has shown potential anti-cancer properties, including the ability to induce apoptosis and inhibit cell cycle progression. However, its clinical application is limited by low solubility and poor bioavailability. In this study, we developed piperine-encapsulated PLGA-b-PEG nanoparticles (Pip-PLNP) using a nanoprecipitation method, which achieved a favorable hydrodynamic diameter of approximately 43.8 ± 0.4 nm to 49.1 ± 0.2 nm and high encapsulation efficiency (∼80 %) in a stable, monodisperse form. The anti-cancer effects of Pip-PLNP were evaluated in HCT116 human colorectal carcinoma cells. MTT assays revealed that Pip-PLNP exhibited significant dose- and time-dependent cytotoxicity, with improved potency compared to free piperine. Apoptosis assays demonstrated that Pip-PLNP induced early and late apoptosis more effectively than free piperine. Additionally, cell cycle analysis showed that Pip-PLNP caused G0/G1 phase arrest, consistent with piperine’s known mechanism of action. In conclusion, Pip-PLNP significantly enhances the anti-cancer efficacy of piperine by improving its bioavailability, cytotoxicity, and apoptotic activity, suggesting its potential as a therapeutic approach for colorectal cancer treatment.