In vitro co-delivery evaluation of PEGylated nano-liposome loaded by glycyrrhizic acid and cisplatin on cancer cell line

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RESEARCH PAPER

In vitro co-delivery evaluation of PEGylated nano-liposome loaded by glycyrrhizic acid and cisplatin on cancer cell lines Ali Hatami & Amir Heydarinasab & Azim Akbarzadehkhiyavi & Farshid Pajoum Shariati

Received: 12 March 2020 / Accepted: 11 August 2020 # Springer Nature B.V. 2020

Abstract Cisplatin, a platinum-based drug, is widely used in cancer treatment but is associated with significant side effects; new treatment delivery methods must be developed which enhance treatment efficiency while decreasing the sequelae of chemotherapy. The aim of this study was to develop novel liposomal nanoparticles (NPs) loaded with two drugs including cisplatin and glycyrrhizic acid. This study hypothesized that introducing glycyrrhizic acid, as an adjuvant treatment, and cisplatin, as a chemotherapeutic agent, into a codelivery system can enhance the therapeutic effect. In this study, the synthetic method and specifications of NPs were evaluated. After surface modification by polyethylene glycol (PEG), the size and the zeta potential of NPs were reported as 81.6 nm and − 30.7 mV, respectively. DLD-1 and LIM-2405 human colon cancer cell lines were then applied to evaluate the cytotoxicity of NPs using an MTT assay. The results revealed that IC50 A. Hatami : A. Heydarinasab (*) : F. P. Shariati Department of Chemical Engineering, Science and Research branch, Islamic Azad University, Tehran, Iran e-mail: [email protected]

A. Hatami e-mail: [email protected] F. P. Shariati e-mail: [email protected] A. Akbarzadehkhiyavi Department of Pilot Nano-biotechnology, Pasteur Institute of Iran, Tehran, Iran e-mail: [email protected]

for DLD-1, as a resistant cell line to cisplatin, decreased by 48% on co-delivery system treatment. Furthermore, to determine the proliferative potential of cell lines and DNA damage on cancerous cells after treatment by NPs and cisplatin in free form, the cell proliferation assay and immunocytochemistry method were performed. The results showed that a co-delivery system caused more than 43% DNA damage to cancerous cells compared with the free form of cisplatin. The finding of this study demonstrates that the co-delivery system has a significant anti-cancer efficiency compared with the free form of cisplatin. To conclude, the results of this study demonstrate a possible application of glycyrrhizic acid as an adjuvant treatment for cisplatin on co-delivery systems.

Keywords Nano-particles . Cisplatin . Glycyrrhizic acid . Co-delivery system . Nano-medicine

Introduction Colorectal cancer (CRC) is the fourth highest cause of cancer-related deaths worldwide (Arnold et al. 2017). Nowadays, common treatments for CRC are radiotherapy, surgery, and chemotherapy (Binefa et al. 2014). Currently, several drugs can be used as anti-cancer chemotherapy for CRC and are generally administered before or after surgery. However, the side effects and long-term damage of chemotherapy are major concerns to both patients and clinicians. Current treatment to

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