期刊
JOURNAL OF CONTROLLED RELEASE
卷 195, 期 -, 页码 147-154出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2014.06.012
关键词
Delivery system; Disulfide; Redox-potential; Thiol-disulfide exchange; Parenteral; Cancer
资金
- Scholarship Fund of the Swiss Chemical Industry (SSCI) [2-70882-08]
Exploiting the redox-sensitivity of disulfide bonds is an increasingly popular means to trigger drug release at a target location in the body. The bio-reducible linker (containing a disulfide) can be cleaved when the drug delivery system in which it is incorporated passes from the poorly reducing extra-cellular biological environments to the strongly reducing intra-cellular spaces. This phenomenon has been characterized for a variety of drug carriers (e.g. anti-body- drug conjugates and nucleic acid carriers) and made use of not only for intra-cellular drug release, but also to provide a mechanism of biodegradation. However, successful therapeutic application of redox-sensitive drug delivery systems, which are mostly investigated in the treatment of cancer, depends on timely cleavage of the disulfide in the body. As a result, an accurate and detailed understanding of the biological redox stimulus and the properties of the redox-sensitive moiety is of importance. This review introduces a number of currently relevant reducing agents and redox enzymes, and provides an overview of the redox environments a disulfide-containing drug delivery system encounters upon parenteral administration. Furthermore, the current state of knowledge regarding the behavior and responsiveness of disulfides in these redox-biological compartments is discussed. (C) 2014 Elsevier B.V. All rights reserved.
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