Folic acid-conjugated biopolymeric nanoparticles for targeted delivery of ixabepilone in breast cancer

Ixabepilone (IXA) is an FDA-approved chemotherapeutic agent for metastatic breast cancer; however, its clinical use is limited by severe toxicity to healthy tissues. To improve its therapeutic index, tumor-targeted drug delivery systems are required. In this study, IXA was encapsulated for the first time into folic acid (FA)-functionalized biopolymeric nanoparticles (NPs) to promote preferential delivery to folate receptor (FR)-expressing breast cancer cells. Chitosan (CS) and alginate (ALG) were conjugated with FA to fabricate targeted NP systems, and IXA-loaded formulations were optimized in terms of encapsulation efficiency and particle size. The optimized IXA/FACS and IXA/FAALG NPs exhibited encapsulation efficiencies of 51.3 ± 4.6% and 47.6 ± 5.0%, with mean particle sizes of approximately 155 nm. <i>In vitro</i> release studies under physiological and tumor-mimicking pH conditions demonstrated pH-responsive behavior, with increased IXA release at acidic pH (5.5). Release kinetics analysis indicated diffusion-controlled and anomalous transport mechanisms according to the Higuchi and Korsmeyer-Peppas models. Cytotoxicity studies on MDA-MB-231 and MCF-7 breast cancer cell lines revealed enhanced cytotoxic effects of FA-conjugated IXA-loaded NPs in FR-positive MDA-MB-231 cells compared to MCF-7 cells, suggesting preferential FR-mediated cellular interaction. Overall, FA-functionalized CS and ALG NPs represent a promising <i>in vitro</i> platform for targeted IXA delivery in FR-expressing breast cancer therapy.