Tunable environmental sensitivity and degradability of nanogels based on derivatives of cystine and poly(ethylene glycols) of various length for biocompatible drug carrier

Add time:08/11/2019    Source:sciencedirect.com

Nanogels are promising carriers for drug delivery, especially when they degrade under conditions typical for cancer cells to release a drug. By using the precipitation polymerization we synthesized a biocompatible and degradable nanogel based on poly(ethylene glycol) methyl ether methacrylate (OEGMA) and di(ethylene glycol) methyl ether methacrylate (MEO2MA) cross-linked with a redox-sensitive linker, N,N′-bis(methacryloyl)cystine – (mBISS). The application of appropriate proportions of monomers during the nanogel synthesis allowed us to set its volume-phase-transition temperature to the body temperature while the aggregation of the nanogel in physiological conditions was eliminated. The presence of carboxylic groups in mBISS made the nanogel sensitive to pH, gave it stability under conditions of high ionic strength and allowed it to bind the anticancer drug – doxorubicin (DOX). The degradation of nanogel was examined by using electron microscopies. In the presence of a high concentration of glutathione (a reducing agent for the -S-S- bridges) which is the case for most cancer cells, the spherical shape of the nanogel and correspondingly its structure were destroyed. The obtained profiles for the release of DOX from the nanogel revealed that the smallest amount of DOX was released from the nanogel at pH 7.4, while under conditions present in most cancer cells, this is at pH 5.0 and cGSH = 40 mM, the highest cumulative release of DOX was observed. The DOX loaded nanogels were cytotoxic against MCF-27 and HT-29 cancer cells similarly to DOX alone. The unloaded gel nanoparticles did not inhibit proliferation of the cells.

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