A Stable and Cleavable <i>O</i>-Linked Spacer for Drug Delivery Systems
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- Ito Kei
- Graduate School of Pharmaceutical Sciences, The University of Tokyo
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- Tatsumi Toshifumi
- Graduate School of Pharmaceutical Sciences, The University of Tokyo
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- Takahashi Kazuki
- Graduate School of Pharmaceutical Sciences, The University of Tokyo
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- Shimizu Yohei
- Graduate School of Pharmaceutical Sciences, The University of Tokyo
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- Yamatsugu Kenzo
- Graduate School of Pharmaceutical Sciences, The University of Tokyo
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- Kanai Motomu
- Graduate School of Pharmaceutical Sciences, The University of Tokyo
Bibliographic Information
- Other Title
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- Communications to the Editor : A Stable and Cleavable O-Linked Spacer for Drug Delivery Systems
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Abstract
<p>Anti-cancer chemotherapy with good efficacy and fewer side effects is highly desirable. A drug delivery system comprising a cancer-targeting module and a cytotoxic agent connected with a cleavable linker is promising for reducing side effects. The development of a cleavable linker satisfying the requirements of both stability and cleavability, however, is difficult, especially when a carbonate moiety is used for conjugating the linker to a hydroxy group in a drug of interest. We herein report a new stable linker comprising carbamate and ester spacers, which can be introduced on a hydroxy group of a drug. This linker is more stable in aqueous neutral buffer than a corresponding carbonate-type linker, and releases a payload anti-cancer drug, SN-38, through a two-step sequence upon cathepsin B treatment. This linker may have potential use in other drug delivery systems to lower side effects by selectively transporting cytotoxic drugs to tumor cells.</p>
Journal
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- Chemical and Pharmaceutical Bulletin
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Chemical and Pharmaceutical Bulletin 68 (3), 212-215, 2020-03-01
The Pharmaceutical Society of Japan