Abstract
In this paper, we describe the development of a redox-responsive delivery system based on 6-mercaptopurine (6-MP)-conjugated colloidal mesoporous silica (CMS) via disulfide bonds. mPEG was modified on the surface of silica to improve the dispersibility and biocompatiblity of CMS by reducing hemolysis and protein adsorption. The CMS carriers with different amounts of thiol groups were prepared to evaluate the impact of modified thiol on the drug loading efficiency. In vitro release studies demonstrated that the CMS nanoparticles exhibited highly redox-responsive drug release. The cumulative release of 6-MP was less than 3% in absence of GSH, and reached more than 70% within 2h in the presence of 3mM GSH. In addition, by comparing the cumulative release profiles of CMS-SS-MP@mPEG with their counterparts without the grafting of hydrophilic PEG, it was found that mPEG chains did not hinder the drug release due to the cleavable disulfide bonds and the improved dispersibility. Overall, this work provides a new strategy to connect thiol-containing/thiolated drugs and hydrophilic polymers to the interior and exterior of silica via disulfide bonds to obtain redox-responsive release and improve the dispersibility and biocompatibility of silica.
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