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PEG-PLGA core–shell nanoparticles for the controlled delivery of picoplatin–hydroxypropyl β-cyclodextrin inclusion complex in triple-negative breast cancer: In vitro and in vivo study

Nafie, Mohamed S., Sedky, Nada K., Hassan, Hatem A. F. M., Fawzy, Iten M., Abdelhady, Manal M. M., Bakowsky, Udo, Fahmy, Sherif Ashraf (2024) PEG-PLGA core–shell nanoparticles for the controlled delivery of picoplatin–hydroxypropyl β-cyclodextrin inclusion complex in triple-negative breast cancer: In vitro and in vivo study. Nanotechnology Reviews, 13 (1). Article Number 20240115. ISSN 2191-9089. E-ISSN 2191-9097. (doi:10.1515/ntrev-2024-0115) (KAR id:108140)

Abstract

In this study, we prepared an inclusion complex of picoplatin (Pc) with 2-hydroxy propyl β cyclodextrin (HPCD) to improve its hydrophilicity, yielding Pc-HPCD. The Pc-HPCD complex was encapsulated into PEG-PLGA nanoparticles (NPs) using the emulsion–solvent evaporation method, yielding Pc-HPCD@PEG-PLGA core–shell NPs. The inclusion complex was assessed using 1HNMR spectroscopy and a phase solubility study. In addition, the average hydrodynamic diameter, polydispersity index, zeta potential, and encapsulation efficiency (EE%) of the Pc-HPCD@PEG-PLGA NPs were 190.2 ± 8.7 nm, 0.14 ± 0.02, −13.97 ± 0.67 mV, and 80.7 ± 2.4%, respectively. In vitro release study showed a pH-triggered release manner. Furthermore, the biological evaluation of Pc-HPCD@PEG-PLGA NPs revealed a significantly potent cytotoxic activity (IC50 = 1.6 ± 0.24 µg/ml) against triple-negative breast cancer cells (TNBC), surpassing that of Pc-HPCD (IC50 = 5.3 ± 0.93 µg/ml) and Pc (IC50 = 7.5 ± 0.4 µg/ml). Pc-HPCD@PEG-PLGA NPs induced significant apoptosis and the ability to arrest cells at the sub-G1 phase in MDA-MB-231 cells. Moreover, in an in vivo model established using SEC-bearing mice, treatment with Pc-HPCD@PEG-PLGA demonstrated significant inhibition of tumor proliferation (67.2%). This was accompanied by improvements in hematological and biochemical measurements, as well as histopathological examination, which indicated a reduction in cellular and nuclear pleomorphism. Our study demonstrated the potential of Pc-HPCD@PEG-PLGA NPs to be employed as an effective and safe therapy capable of conquering TNBC.

Item Type: Article
DOI/Identification number: 10.1515/ntrev-2024-0115
Uncontrolled keywords: cell cycle arrest; hydroxypropyl-β-cyclodextrin; apoptosis; PEG-PLGA nanoparticles; inclusion complex; picoplatin; cytotoxicity; triple-negative breast cancer (MDA-MB-231)
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Funders: Alexander von Humboldt Foundation (https://ror.org/012kf4317)
Philipps University of Marburg (https://ror.org/01rdrb571)
SWORD Depositor: JISC Publications Router
Depositing User: JISC Publications Router
Date Deposited: 12 Dec 2024 16:35 UTC
Last Modified: 13 Dec 2024 11:05 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/108140 (The current URI for this page, for reference purposes)

University of Kent Author Information

Hassan, Hatem A. F. M..

Creator's ORCID: https://orcid.org/0009-0009-7493-8564
CReDIT Contributor Roles: Investigation, Methodology, Writing - review and editing, Formal analysis, Data curation, Software, Writing - original draft
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