Design, Synthesis, and Characterization of Schiff Base Bond-Linked pH-Responsive Doxorubicin Prodrug Based on Functionalized mPEG-PCL for Targeted Cancer Therapy

Polymers

Xinhui Wang¹  Dianyu Wang¹  Wei Sun¹  Yinglei Zhai¹  Zhiqiang Zhang²  Xing Zhou³  Lei Zhang⁴ 

[1] Department of Biomedical Engineering, School of Medical Devices, Shenyang Pharmaceutical University, Shenyang 110016, China;Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China;Hainan Institute of Materia Medica, Haikou 570311, China;Shanghai Pharma Group (Benxi) Northern Pharmaceutical Co., Ltd., Benxi 117004, China;

关键词: doxorubicin;    pH-sensitive;    prodrug;    micelles;    imine;   

DOI  :  10.3390/polym10101127

来源: DOAJ

【 摘 要 】

The side effects of doxorubicin (DOX) extremely limit its application in the treatment of malignant tumors. Nano-sized polymeric drugs based on the acidic microenvironment of tissular- or intra- tumor have attracted ample attention because of their potential in reducing side effects. In this research, an amphiphilic diblock copolymer based on poly (ethylene glycol) (PEG) and functionalized polycaprolactone (PCL) was synthesized and utilized as the drug carrier. DOX was chemically conjugated with the polymer via acid-cleavable imine bonds to obtain a novel pH-sensitive DOX prodrug (mPEG-PCL-Imi-DOX). mPEG-PCL-Imi-DOX (24.2 wt % DOX content) formed micelles with an average diameter of 125 nm through a simple solvent evaporation method. The in vitro release profile demonstrated that DOX release of the prodrug micelles was pH-responsive and able to be accelerated with the decrease of pH. In vitro cytotoxicity assay tests revealed that the pH-sensitive DOX prodrug micelles exhibited relatively lower toxicity and similar antitumor efficacy towards MCF-7 cells compared with free DOX. Hence, the DOX prodrug micelles with imine bonds can offer a carrier with great potential for chemo-therapeutics.

【 授权许可】

Unknown