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

  • Int J Biol Macromol. 2026 Apr:354:151390. doi: 10.1016/j.ijbiomac.2026.151390.
Ayça Mehmetoğlu Al  1 ,  İskender Ince  2 ,  Necmettin Özdemir  3 ,  Erkan Kahraman  4 ,  Erdem Göker  5 ,  Yeliz Yildirim  6
Affiliations
  • 1. Department of Biotechnology, Graduate School of Natural and Applied Science, Ege University, Izmir, Turkey.
  • 2. Center for Drug R&D and Pharmacokinetic Applications (ARGEFAR), Ege University, Izmir, Turkey; Department of Nuclear Applications, Institute of Nuclear Sciences, Ege University, İzmir, Turkey. Electronic address: [email protected].
  • 3. Department of Medical Pathology, Ege University Faculty of Medicine, İzmir, Turkey.
  • 4. Center for Drug R&D and Pharmacokinetic Applications (ARGEFAR), Ege University, Izmir, Turkey; Atatürk Vocational School of Health Services, Ege University, Izmir, Turkey.
  • 5. Center for Drug R&D and Pharmacokinetic Applications (ARGEFAR), Ege University, Izmir, Turkey; Department of Medical Oncology, Ege University Faculty of Medicine, Izmir, Turkey.
  • 6. Center for Drug R&D and Pharmacokinetic Applications (ARGEFAR), Ege University, Izmir, Turkey; Faculty of Science, Department of Chemistry, Ege University, Izmir, Turkey. Electronic address: [email protected].
PMID: 41825671 DOI: 10.1016/j.ijbiomac.2026.151390
Abstract

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.

Keywords
Blend Nanoparticle; IVIS image system; Ixabepilone; MCF-7 cell line; MDA-MB-231 cell line; Targeted Drug Delivery.
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