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

Sussana A. Elkassih, Petra Kos, Hu Xiong, Daniel J Siegwart

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)607-617
Number of pages11
JournalBiomaterials Science
Volume7
Issue number2
DOIs
StatePublished - Feb 1 2019

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ASJC Scopus subject areas

  • Biomedical Engineering
  • Materials Science(all)

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