Folic acid-targeted chitosan-alginate blend nanoparticles for enhanced ixabepilone delivery and antitumor efficacy in breast cancer.

Ixabepilone (IXA) is a potent antineoplastic agent capable of overcoming tumor resistance in breast cancer; however, its clinical utility is limited by systemic toxicity and off-target effects. To address these limitations, IXA-loaded blend nanoparticles combining the advantages of targeted FACS and FAALG polymer systems (FACS-FAALG blend NPs) were developed and comprehensively characterized. The nanoparticles exhibited a mean size of 218.17 ± 6.9 nm and an encapsulation efficiency of 53.7 ± 7.7%. In vitro release studies conducted at pH 5.5, 6.5, and 7.4 demonstrated pH-responsive behavior, with the highest cumulative release (85.0%) observed at pH 5.5. Cytotoxicity assays performed on MCF-7 and MDA-MB-231 cells revealed that IXA-loaded blend NPs induced greater reductions in cell viability and enhanced cellular uptake in MDA-MB-231 cells compared to the free drug. In vivo antitumor studies in nude mice bearing MDA-MB-231 tumors showed that IXA/FACS-FAALG blend NPs significantly inhibited tumor growth compared to non-targeted CS-ALG blend NPs. Folic acid-mediated targeting improved tumor accumulation, biodistribution, and therapeutic efficacy, as supported by IVIS imaging. Overall, this blended nanoparticle platform represents a formulation approach for targeted IXA delivery and shows potential for further investigation in breast cancer models.