Preparation and Evaluation of Chitosan Coated PLGA Nanoparticles Encapsulating Ivosidenib with Enhanced Cytotoxicity Against Human Liver Cancer Cells
Bader B. Alsulays, Alhussain Aodah, Mohammad Ahmed, Md. Khalid Anwer
Abstract
Purpose: Ivosidenib (IVO), an isocitrate dehydrogenase-1 (IDH1) used for treatment of acute myeloid leukemia (AML) and cholangiocarcinoma. However, poor solubility, low bioavailability, high dose and side effects limit clinical application of IVO. Methods: Ivosidenib-loaded PLGA nanoparticles (IVO-PLGA-NPs) and Ivosidenib-loaded chitosan coated PLGA nanoparticles (IVO-CS-PLGA-NPs) were prepared using emulsification and solvent evaporation method for the treatment of liver cancer. Results: The developed IVO-PLGA-NPs were evaluated for their particle size (171.7± 4.9 nm), PDI (0.333), ZP (− 23.0± 5.8 mV), EE (96.3± 4.3%), and DL (9.66± 1.1%); similarly, the IVO-CS-PLGA-NPs were evaluated for their particle size (177.3± 5.2 nm), PDI (0.311), ZP +25.9± 5.7 mV, EE (90.8± 5.7%), and DL (9.42± 0.7%). The chitosan coating of IVO-PLGA-NPs was evidenced by an increase in mean particle size and positive ZP value. Because of the chitosan coating, the IVO-CS-PLGA-NPs showed a more stable and prolonged release of IVO than IVO-PLGA-NPs. In comparison to pure-IVO, the IVO-PLGA-NPs and IVO-CS-PLGA-NPs were found to be more effective against HepG2 cells, with IC 50 values for the MTT assay being approximately half of those of pure-IVO. In HepG2 cells, the expressions of caspase-3, caspase-9, and p53 were significantly (p < 0.05) elevated. Conclusion: Overall, these findings suggest that chitosan coating of IVO-PLGA-NPs improves the delivery and efficacy of ivosidenib in liver cancer treatment. Keywords: polymers, characterization, bioavailability, sustained release, caspase