Preparation and Evaluation of Chitosan Coated PLGA Nanoparticles Encapsulating Ivosidenib with Enhanced Cytotoxicity Against Human Liver Cancer Cells

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 IC₅₀ 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

Acknowledgments

The authors extend their appreciation to the Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia for funding this research through the project number (IF2/PSAU-2022/03/22082).

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

The authors extend their appreciation to the Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia for funding this research through the project number (IF2/PSAU-2022/03/22082).