Switching indication of PEGylated lipid nanocapsules-loaded with rolapitant and deferasirox against breast cancer: Enhanced in-vitro and in-vivo cytotoxicity

Mohamed Fawzi Kabil; Mohamed Y Mahmoud; Alaa F Bakr; Dalia Zaafar; Ibrahim M El-Sherbiny

doi:10.1016/j.lfs.2022.120731

Switching indication of PEGylated lipid nanocapsules-loaded with rolapitant and deferasirox against breast cancer: Enhanced in-vitro and in-vivo cytotoxicity

Life Sci. 2022 Sep 15:305:120731. doi: 10.1016/j.lfs.2022.120731. Epub 2022 Jun 24.

Authors

Mohamed Fawzi Kabil¹, Mohamed Y Mahmoud², Alaa F Bakr³, Dalia Zaafar⁴, Ibrahim M El-Sherbiny⁵

Affiliations

¹ Nanomedicine Research Labs, Center for Materials Science, Zewail City of Science and Technology, 6th of October City, Giza, Egypt.
² Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
³ Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
⁴ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt.
⁵ Nanomedicine Research Labs, Center for Materials Science, Zewail City of Science and Technology, 6th of October City, Giza, Egypt. Electronic address: ielsherbiny@zewailcity.edu.eg.

PMID: 35753435
DOI: 10.1016/j.lfs.2022.120731

Abstract

Breast cancer (BC) is considered the leading cause of mortality and morbidity among adult women worldwide, and it is associated with many genetic or hormonal factors. Despite the advanced therapeutic and theranostic strategies for BC treatment, cancer metastasis and relapse are often observed among patients which lead to therapeutic failure. Accordingly, among the repositioned medication against BC proliferation is neurokinin receptor antagonists and iron chelating agents especially rolapitant HCl (RP) and deferasirox (DFO), respectively. However, RP and DFO are classified as class II with low aqueous solubility. Both drugs were nanoformulated into PEGylated lipid nanocapsules (LNCs) for enhancing their aqueous solubility and augmenting their efficacy. RP-LNCs, DFO-LNCs and their combinations were evaluated according to particle size (PS), zeta potential, polydispersity index (PDI) and surface morphology. Importantly, the antitumor effect of these novel molecules and their nanoforms was evaluated against the suppression of Ehrlich Ascites tumor model using female mice. Results revealed that RP-LNCs, DFO-LNCs and RP/DFO-LNCs exerted PS from 45.23 ± 3.54 to 60.1 ± 3.32 nm with PDI around 0.20 which indicates homogenous particles distribution. Also, RP-LNCs, DFO-LNCs and RP/DFO-LNCs displayed surface charges of +16.6 ± 6.9, -13.3 ± 5.82 and - 20.2 ± 5.40 mV, respectively. The obtained LNCs conferred a high potent cytotoxic effect against MCF7 cancer cells as compared to parent drugs, with IC₅₀ of 10.86 ± 0.89, 3.34 ± 0.99 and 2.24 ± 0.97 μg/mL for RP-LNCs, DFO-LNCs and RP/DFO-LNCs, respectively. The in-vivo pharmacodynamics effect of the developed nano-formulations showed superior antitumor effect for the individual drugs rather than their combinations as compared to the control group. The current study confirmed the potential of RP and DFO nanoforms as promising therapeutic agents for BC treatment.

Keywords: Breast cancer; Cytotoxicity; Deferasirox; PEGylated lipid nanocapsules; Rolapitant.

MeSH terms

Animals
Breast Neoplasms* / drug therapy
Breast Neoplasms* / pathology
Deferasirox / pharmacology
Female
Humans
Lipids / therapeutic use
Mice
Nanocapsules*
Neoplasm Recurrence, Local / drug therapy
Polyethylene Glycols / therapeutic use
Spiro Compounds

Substances

Lipids
Nanocapsules
Spiro Compounds
Polyethylene Glycols
rolapitant
Deferasirox