Document Type : Research Article
Authors
1
Department of Chemistry, Tabriz Branch, Islamic Azad University, Tabriz, Iran
2
Department of Chemistry, Tabriz Branch, Islamic Azad University, Tabriz, IRAN
3
Department of Medicinal Chemistry, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
4
Department of Medical Nanotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran
5
Physiology Research Center and Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
Abstract
In the recent decade, the design and engineering of novel drug delivery systems based on biodegradable nanoparticles using biocompatible polymers like poly (ε-caprolactone)/poly(ethylene glycol)/poly(ε-caprolactone) triblock copolymer (PCEC) attracted many attentions. These nanocarriers have shown high potentials in enhancing treatment efficiency and minimizing the side effects of drugs. Besides, combination therapy has become a potential approach for cancer treatment with synergistic impacts. For the first time, we investigated co-delivery of the antitumor drug, doxorubicin (DOX), and ezetimibe (EZ) as a cholesterol uptake-blocking drug with PCEC on prostate cancer cell line (PC3). The PCEC was synthesized by ring-opening polymerization of ε-CL initiated by PEG2000. The obtained copolymer was characterized by Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H-NMR) spectroscopy, and gel permeation chromatography (GPC). In this study, DOX and EZ were encapsulated within PCEC by double and simple emulsion techniques, which led to the preparation of DOX@PCEC, EZ@PCEC, and DOX+EZ@PCEC nanoparticles. The size and morphology of the developed nanoparticles were analyzed by field emission scanning electron microscopy (FE-SEM). Also, the particle size and zeta potential of the drug-loaded PCEC nanoparticles were determined by dynamic light scattering (DLS) analysis . The release behavior of DOX and EZ from nanoparticles at two pH values and temperatures was evaluated. The cytotoxicity of nanoparticles was demonstrated by MTT assay using PC3 prostate cancer cell line. Based on the MTT assay results, PCEC copolymer exhibited negligible cytotoxicity on the growth of the PC3 cell line. Therefore, PCEC is a biocompatible and suitable nano-vehicle for this study. Moreover, the cytotoxic activity of all formulations was dose-dependent. The cytotoxic effect of DOX+EZ@PCEC nanoparticles against PC3 cell line was higher than single drug@PCEC nanoparticles. All data confirmed that the EZ as a cholesterol-lowering drug showed a synergistic effect in combination with DOX as an anticancer drug. Finally, the results showed a successful formulation of DOX+EZ@PCEC nanoparticles with high efficiency in prostate cancer treatment.
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