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

Publication date: 15 August 2019Source: International Journal of Pharmaceutics, Volume 567Author(s): 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 TsaiAbstractStimuli-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 ...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research