title: PEGylated mesoporous silica as a redox-responsive drug delivery system for loading thiol-containing drugs.
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.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, PR China.
authors.forename: Qinfu
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Physiology, School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, PR China.
authors.forename: Jiahong
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Medical Devices, Shenyang Pharmaceutical University, PR China.
authors.forename: Yikun
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, PR China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, PR China.
authors.forename: Tongying
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning Province 110016, PR China. Electronic address: silingwang@syphu.edu.cn.
authors.forename: Siling
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D004220:Disulfides / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D004339:Drug Compounding; D065546:Drug Liberation; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D015122:Mercaptopurine / Q000008:administration & dosage* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D010084:Oxidation-Reduction; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011817:Rabbits; D012822:Silicon Dioxide / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D004220:Disulfides; D004337:Drug Carriers; D011092:Polyethylene Glycols; D012822:Silicon Dioxide; C028210:monomethoxypolyethylene glycol; D015122:Mercaptopurine
keywords: 6-Mercaptopurine; Colloidal mesoporous silica; Disulfide bonds; Methoxy polyethylene glycols; Redox-responsive