Preparation, characterization, and Co-delivery of cisplatin and doxorubicin-loaded liposomes to enhance anticancer Activities

Mahdi Bahrami Parsa; Farzaneh Tafvizi; Vahid Chaleshi; Mostafa Ebadi

doi:10.1016/j.heliyon.2023.e20657

Preparation, characterization, and Co-delivery of cisplatin and doxorubicin-loaded liposomes to enhance anticancer Activities

Heliyon. 2023 Oct 5;9(10):e20657. doi: 10.1016/j.heliyon.2023.e20657. eCollection 2023 Oct.

Authors

Mahdi Bahrami Parsa¹, Farzaneh Tafvizi¹, Vahid Chaleshi², Mostafa Ebadi³

Affiliations

¹ Department of Biology, Parand Branch, Islamic Azad University, Parand, Iran.
² Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Disease, Shahid Beheshti University of Medical Science, Tehran, Iran.
³ Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran.

Abstract

Ovarian cancer stands as a leading cause of cancer-related deaths among women globally. This malignancy has hindered successful treatment attempts due to its inherent resistance to chemotherapy agents. The utilization of cisplatin and doxorubicin-loaded liposomes emerges as a strategically advantageous approach in the realm of biomedical applications. This strategy holds promise for augmenting drug efficacy, mitigating toxicity, refining pharmacokinetics, and facilitating versatile drug delivery while accommodating combination therapies. In pursuit of scholarly investigations, the eminent databases, including PubMed/MEDLINE, ScienceDirect, Scopus, and Google Scholar, were meticulously scrutinized. Within this study, a nano-liposomal formulation was meticulously designed to serve as a co-delivery system. This system was optimized by varying lipid concentrations, hydration time, and DSPC: cholesterol molar ratios to efficiently encapsulate and load doxorubicin (DOX) and cisplatin (CIS) to overcome drug resistance problems. The Lipo (CIS + DOX) formulation underwent rigorous characterization including dimensions, entrapment efficiencies and drug release kinetics. Notably, the entrapment efficiency of cisplatin and doxorubicin loaded liposomal nanoparticles was an impressive 85.29 ± 1.45 % and 73.62 ± 1.70 %, respectively. Furthermore, Lipo (CIS + DOX) drug release kinetics exhibited pH-dependent properties, with lower drug release rates at physiological pH (7.4) than acidic (pH 5.4). Subsequent cytotoxicity assays revealed the enhanced biocompatibility of dual-drug liposomes with HFF cells compared to free drug combinations. Impressively, CIS and DOX-loaded liposomes induced significant cytotoxicity against A2780 in comparison to free drugs and combinatorial free drugs. Furthermore, the CIS and DOX-loaded liposome showed induced apoptotic potential and cell cycle arrest in A2780 compared to CIS, DOX, and their combination (CIS + DOX). Combining CIS and DOX via liposomal nanoparticles introduces a promising therapeutic avenue for addressing ovarian cancer. These nano-scale carriers hold the potential for attenuating the untoward effects of singular drugs and their attendant toxicities.

Keywords: A2780 cell line; Apoptosis; Cisplatin; Co-delivery; Doxorubicin; Liposome.