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pH-Responsive PEGylated Niosomal Nanoparticles as an Active-Targeting Cyclophosphamide Delivery System for Gastric Cancer Therapy

Lookup NU author(s): Professor Yen Nee Tan

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

A PEGylated niosomal formulation of cyclophosphamide (Nio-Cyclo-PEG) was prepared using a central composite design and characterized in terms of drug loading, size distribution, and average size. The stability of formulations was also studied at different conditions. In vitro cytotoxicity of drug delivery formulations was assessed on gastric cancer cells using MTT assay. The mechanism of cytotoxicity was studied at the transcriptional level by real-time PCR on Caspase3, Caspase9, CyclinD, CyclinE, MMP-2, and MMP-9 genes, while apoptosis was investigated with flow cytometry. The anti-metastatic property was evaluated using the scratch method. Propidium iodide staining was used to study the cell cycle. The results indicated that the as-designed nanocarrier exhibited a controlled drug release pattern with improved nanoparticle stability. It was found that the living cancer cells treated with Nio-Cyclo-PEG showed a significant decrease in number when compared with the niosomal carrier without PEG (Nio-Cyclo) and free drug (Cyclo). Moreover, the drug-loaded nanocarrier induced planned death (apoptosis) in the cancer cells through the regulation of Caspase3, Caspase9, CyclinD, CyclinE, MMP-9, and MMP-2 gene expression, indicating that the Nio-Cyclo-PEG formulation could significantly inhibit the cell cycle at the sub G1 phase as well as prevent the migration of cancer cells. In conclusion, Nio-Cyclo-PEG as developed in this study could serve as an active-targeting drug delivery nanocarriers for gastric cancer therapy with high efficacy and minimal side effects on healthy tissues/cells.

Publication metadata

Author(s): Khodabakhsh F, Bourbour M, Yaraki MT, Bazzazan S, Bakhshandeh H, Ahangari Cohan R, Tan YN

Publication type: Article

Publication status: Published

Journal: Molecules

Year: 2022

Volume: 27

Issue: 17

Online publication date: 24/08/2022

Acceptance date: 18/08/2022

Date deposited: 20/09/2022

ISSN (electronic): 1420-3049

Publisher: MDPI

URL: https://doi.org/10.3390/molecules27175418

DOI: 10.3390/molecules27175418

PubMed id: 36080186

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