Nanodelivery and anticancer effect of a limonoid, nimbolide, in breast and pancreatic cancer cells

Introduction: Nimbolide (Nim), a limonoid obtained from the neem tree, Azadirachta indica, has several pharmacological properties, including anticancer effects in different type of cancers. No drug-delivery system has been reported for enhancing the therapeutic application of this novel hydrophobic molecule. Methods: In the present research, poly(lactic-co-glycolic acid) (PLGA) nanoparticles of Nim (Nim-nano) were formulated by nanoprecipitation, characterized for physicochemical properties, and screened for anticancer potential in breast (MCF-7 and MDA-MB-231) and pancreatic (AsPC-1) cancer cell lines. Results: The Nim-nano had a particle size of 183.73 +/- 2.22 nm and 221.20 +/- 11.03 nm before and after lyophilization, respectively. Cryoprotectants (mannitol and sucrose) significantly inhibited growth in particle size due to lyophilization. The zeta-potential of the Nim-nano was -22.40 +/- 4.40 mV. Drug loading and encapsulation efficiency of Nim-nano were 5.25%+/- 1.12% and 55.67% +/- 12.42%, respectively. The Nim-nano exhibited sustained release of Nim for more than 6 days in PBS (pH 7.4) and showed two- to three-fold enhanced cytotoxicity in breast and pancreatic cancer cell lines compared with free Nim. Conclusion: The Nim-nano formulation has great potential for treatment of cancers, such as pancreatic and breast cancer. Further, the PLGA-polymer surface can be modified by conjugation with polyethylene glycol, receptor-binding ligands (eg, folic acid), and other that which may lead to targeted delivery of Nim in the treatment of cancer.