Fabrication of redox-responsive Bi(mPEG-PLGA)-Se2 micelles for doxorubicin delivery

Yihenew Simegniew Birhan; Balkew Zewge Hailemeskel; Tefera Worku Mekonnen; Endiries Yibru Hanurry; Haile Fentahun Darge; Abegaz Tizazu Andrgie; Hsiao-Ying Chou; Juin-Yih Lai; Ging-Ho Hsiue; Hsieh-Chih Tsai

doi:10.1016/j.ijpharm.2019.118486

Fabrication of redox-responsive Bi(mPEG-PLGA)-Se₂ micelles for doxorubicin delivery

Int J Pharm. 2019 Aug 15:567:118486. doi: 10.1016/j.ijpharm.2019.118486. Epub 2019 Jun 28.

Affiliations

¹ Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, Taiwan, ROC.
² Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, Taiwan, ROC; Advanced Membrane Materials Center, National Taiwan University of Science and Technology, Taipei 106, Taiwan, ROC; R&D Center for Membrane Technology, Chung Yuan Christian University, Chungli, Taoyuan 320, Taiwan, ROC.
³ Department of Chemical Engineering, National Chung Hsing University, Taichung 402, Taiwan, ROC. Electronic address: ghhsiue@mx.nthu.edu.tw.
⁴ Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, Taiwan, ROC; Advanced Membrane Materials Center, National Taiwan University of Science and Technology, Taipei 106, Taiwan, ROC. Electronic address: h.c.tsai@mail.ntust.edu.tw.

PMID: 31260783
DOI: 10.1016/j.ijpharm.2019.118486

Abstract

Stimuli-responsive polymeric nanostructures have emerged as potential drug carriers for cancer therapy. Herein, we synthesized redox-responsive diselenide bond containing amphiphilic polymer, Bi(mPEG-PLGA)-Se₂ from mPEG-PLGA and 3,3'-diselanediyldipropanoic acid (DSeDPA) using DCC/DMAP as coupling agents. Due to its amphiphilic nature, Bi(mPEG-PLGA)-Se₂ self-assembled in to stable micelles in aqueous solution with a hydrodynamic size of 123.9 ± 0.85 nm. The Bi(mPEG-PLGA)-Se₂ micelles exhibited DOX-loading content (DLC) of 6.61 wt% and encapsulation efficiency (EE) of 54.9%. The DOX-loaded Bi(mPEG-PLGA)-Se₂ micelles released 73.94% and 69.54% of their cargo within 72 h upon treatment with 6 mM GSH and 0.1% H₂O₂, respectively, at pH 7.4 and 37 °C. The MTT assay results demonstrated that Bi(mPEG-PLGA)-Se₂ was devoid of any inherent toxicity and the DOX-loaded micelles showed pronounced antitumor activities against HeLa cells, 44.46% of cells were viable at maximum dose of 7.5 µg/mL. The cellular uptake experiment further confirmed the internalization of DOX-loaded Bi(mPEG-PLGA)-Se₂ micelles and endowed redox stimuli triggered drug release in cytosol and nuclei of cancer cells. Overall, the results suggested that the smart, biocompatible Bi(mPEG-PLGA)-Se₂ copolymer could serve as potential drug delivery biomaterial for the controlled release of hydrophobic drugs in cancer cells.

Keywords: Anticancer drug delivery; Diselenide bond; Polymeric micelles; Redox-responsive.

MeSH terms

Antibiotics, Antineoplastic / administration & dosage*
Antibiotics, Antineoplastic / chemistry
Cell Line
Cell Survival / drug effects
Doxorubicin / administration & dosage*
Doxorubicin / chemistry
Drug Delivery Systems*
Drug Liberation
Humans
Micelles
Oxidation-Reduction
Polyesters / administration & dosage*
Polyesters / chemistry
Polyethylene Glycols / administration & dosage*
Polyethylene Glycols / chemistry

Substances

Antibiotics, Antineoplastic
Micelles
Polyesters
methoxypolyethyleneglycol-poly(lactic-co-glycolic acid)
Polyethylene Glycols
Doxorubicin