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Repurposed Axitinib delivered via lipid-extruded PEGylated liposomes: 2D/3D breast cancer cell evaluation and in-vivo pharmacokinetics.

Created on 07 Aug 2026

Authors

Avinash Pawar, Ekta Pardhi, Sumedh Bahadure, Rati Yadav, Santanu Basak, Essha Chatterjee, Santosh Kumar Guru, Neelesh Kumar Mehra

Published in

Journal of liposome research. Pages 1-26. Aug 06, 2026. Epub Aug 06, 2026.

Abstract

PEGylated liposomal nanocarriers have emerged as a promising drug delivery platform for improving the pharmacokinetic performance and systemic circulation of poorly water-soluble anticancer drugs. In this study, Axitinib-loaded PEGylated liposomes (F11-PEGliposome) were prepared and evaluated for the potential treatment of breast cancer. Liposomes were prepared by optimization with a Box-Behnken design and subsequently extruded using lipid extrusion to obtain a vesicle size of 158.6 ± 2.4 nm, PDI of 0.12 ± 0.01, zeta potential of -1.2 ± 0.5, and entrapment efficiency of 79.9 ± 1.8%. In 2D cell culture studies, F11-PEGliposome showed enhanced anticancer activity with IC50 values of 1.7- and 2.13-fold lower than free Axitinib. Cellular uptake, ROS generation, JC-1 mitochondrial membrane potential, and AO/EB staining assays exhibited enhanced internalization and apoptosis induction. In 3D spheroid models, F11-PEGliposome exhibited deep penetration in the tumor, significant growth inhibition, increased ROS production, and pronounced apoptotic cell death. In-vivo pharmacokinetic and biodistribution studies showed extended circulation, enhanced bioavailability, and prolonged half-life. Reduced hepatic and renal toxicity was evident as shown by histopathological evaluation and decreased serum AST, ALT, creatinine, and BUN levels. Western blot analysis revealed dose-dependent increases of cleaved caspase-3 and cleaved PARP1, supporting the conclusion of apoptosis.

PMID:
42560845
Bibliographic data and abstract were imported from PubMed on 07 Aug 2026.

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