KEY TAKEAWAYS
- The study aimed to enhance ivosidenib’s efficacy in liver cancer patients by preparing IVO-PLGA-NPs and IVO-CS-PLGA-NPs to address solubility and bioavailability.
- The study found that chitosan-coated IVO-PLGA-NPs enhance ivosidenib delivery and efficacy in liver cancer treatment.
Ivosidenib (IVO), targeting isocitrate dehydrogenase-1 (IDH1), is utilized in acute myeloid leukemia (AML), cholangiocarcinoma, and liver cancer. Nonetheless, challenges like poor solubility, low bioavailability, high dose requirements, and side effects restrict its clinical utility.
Bader B. Alsulays and the team aimed to enhance ivosidenib’s therapeutic efficacy for liver cancer by developing Ivosidenib-loaded PLGA nanoparticles (IVO-PLGA-NPs) and Ivosidenib-loaded chitosan-coated PLGA nanoparticles (IVO-CS-PLGA-NPs) to overcome solubility and bioavailability challenges.
In the study, researchers prepared IVO-PLGA-NPs and IVO-CS-PLGA-NPs via the emulsification and solvent evaporation method for liver cancer treatment.
The developed IVO-PLGA-NPs were assessed, showing a particle size of 171.7±4.9 nm, PDI of 0.333, ZP of -23.0±5.8 mV, EE of 96.3±4.3%, and DL of 9.66±1.1%. Similarly, IVO-CS-PLGA-NPs displayed a particle size of 177.3±5.2 nm, PDI of 0.311, ZP of +25.9±5.7 mV, EE of 90.8±5.7%, and DL of 9.42±0.7%.
An increase in mean particle size and positive ZP value confirmed the chitosan coating of IVO-PLGA-NPs. Due to the chitosan coating, IVO-CS-PLGA-NPs exhibited a more stable and prolonged release of IVO than IVO-PLGA-NPs.
Compared to pure-IVO, IVO-PLGA-NPs, and IVO-CS-PLGA-NPs demonstrated increased efficacy against HepG2 cells, with IC50 values for the MTT assay approximately half of those of pure-IVO. Moreover, in HepG2 cells, caspase-3, caspase-9, and p53 expressions were significantly (P< 0.05) elevated.
The results indicated that the chitosan coating of IVO-PLGA-NPs enhances the delivery and effectiveness of ivosidenib in liver cancer treatment.
Funding was provided by the Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia.
Source: https://pubmed.ncbi.nlm.nih.gov/38617799/
Alsulays BB, Aodah AH, Ahmed MM, et al. (2024) “Preparation and Evaluation of Chitosan Coated PLGA Nanoparticles Encapsulating Ivosidenib with Enhanced Cytotoxicity Against Human Liver Cancer Cells.” Int J Nanomedicine. 2024 Apr 9;19:3461-3473. doi: 10.2147/IJN.S452989. PMID: 38617799; PMCID: PMC11015841.