Issue 2, 2019

Degradable redox-responsive disulfide-based nanogel drug carriers via dithiol oxidation polymerization

Abstract

Stimuli-responsive nanogels are important drug and gene carriers that mediate the controlled release of therapeutic molecules. Herein, we report the synthesis of fully degradable disulfide cross-linked nanogel drug carriers formed by oxidative radical polymerization of 2,2′-(ethylenedioxy)diethanethiol (EDDET) as a monomer with different cross-linkers, including pentaerythritol tetramercaptoacetate (PETMA). Because the poly(EDDET) backbone repeat structure and cross-linking junctions are composed entirely of disulfide bonds, these nanogels specifically degrade to small molecule dithiols intracellularly in response to the reducing agent glutathione present inside of cells. Cross-linked nanogels were synthesized using controlled microfluidic mixing in the presence of a nonionic Pluronic surfactant PLU-127 to increase the nanogel stability. Adjusting the monomer to cross-linker ratio from 5 : 1 to 100 : 1 (mol/mol) tuned the cross-linking density, resulting in swelling ratios from 1.65 to >3. Increasing the amount of stabilizing Pluronic surfactant resulted in a decrease of nanogel diameter, as expected due to increased surface area of the resulting nanogels. The monomer to cross-linker ratio in the feed had no effect on the formed nanogel diameter, providing a way to control cross-linking density with constant nanogel size but tunable drug release kinetics. Nanogels exhibited an entrapment efficiency of up to 75% for loading of Rhodamine B dye. In vitro studies showed low cytotoxicity, quick uptake, and fast degradation kinetics. Due to the ease of synthesis, rapid gelation times, and tunable functionality, these non-toxic and fully degradable nanogels offer potential for use in a variety of drug delivery applications.

Graphical abstract: Degradable redox-responsive disulfide-based nanogel drug carriers via dithiol oxidation polymerization

Supplementary files

Article information

Article type
Paper
Submitted
11 Ndz 2018
Accepted
09 Huk 2018
First published
12 Huk 2018

Biomater. Sci., 2019,7, 607-617

Author version available

Degradable redox-responsive disulfide-based nanogel drug carriers via dithiol oxidation polymerization

S. A. Elkassih, P. Kos, H. Xiong and D. J. Siegwart, Biomater. Sci., 2019, 7, 607 DOI: 10.1039/C8BM01120F

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