- PEGylated mesoporous silica as a redox-responsive drug delivery system for loading thiol-containing drugs
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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 2 h in the presence of 3 mM 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.
- Zhao, Qinfu,Wang, Chen,Liu, Ying,Wang, Jiahong,Gao, Yikun,Zhang, Xiaojing,Jiang, Tongying,Wang, Siling
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- NMR studies of tautomerism and protonation patterns in bis(6-purinyl) disulfide and ionic forms of 6-mercaptopurine
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1H-13C and 1H-15N HMBC-NMR spectroscopy was applied to study tautomerism and the protonation patterns in 6-mercaptopurine (6mpH) derivatives: bis(6-purinyl) disulfide ((6puS) 2), 6-mercaptopurinium cation (6mpH2+) and purine-6-thiolate anions (6mp-, 6mp-deH2-). 1H, 13C, 15N resonances were assigned and the respective δ1H, δ13C, δ15N chemical shifts as well as JHC, JHN coupling constants determined. Quantum-chemical NMR calculations by GIAO method (B3LYP/6-31G**// RHF/6-31G*) allowed to evaluate the ratio of N(1), N(3), N(7), N(9)H:N(1), N(3), N(7)H, N(9) tautomeric forms for the DMSO-solvated (6puS)2 molecules as ca. 9:1. The existence of "semi-protonated" 6mpH·H3O+ species, intermediate between 6mpH and 6mpH2+, and readily oxidized to (6puS)2 was suggested in the DMSO-d6 + HCl solution. Further hydrolysis and oxidation of the formed disulfide lead to the derivatives of purine-6-sulfenic and purine-6-sulfinic acid.
- Pazderski,Tousek,Sitkowski,Kozerski,Szlyk
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p. 193 - 210
(2008/03/12)
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- SELENOTRISULPHIDES FROM MERCAPTOPURINES
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Products from the reaction of selenium dioxide with 2-mercapto-(2-MP) and 6-mercapto-purines (6-MP) were studied.The molar ratio of selenium dioxide to mercaptopurines was evaluated from u.v. absorption spectra obtained according to a modification of the method of continuous variations.From the results of the stochiometric calculations the products were shown to be seleno-trisulphides and -disulphides.From electrophoretic data equilibrium constans were computed for both reactions.In the presence of an excess of 6-(MP) the derived selenotrisulphide was stable in alkaline solution.
- Czauderna, Marian,Samochocka, Krystyna
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p. 765 - 768
(2007/10/02)
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