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ID 116466
Author
Tsukigawa, Kenji Sojo University
Imoto, Shuhei Sojo University
Yamasaki, Keishi Sojo University
Nishi, Koji Sojo University
Tsutsumi, Toshihiko Kyushu University of Health and Welfare
Yokoyama, Shoko Kyushu University of Health and Welfare
Otagiri, Masaki Sojo University
Keywords
pirarubicin (THP)
human serum albumin (HSA)
HSA-drug conjugates
pH-sensitive
drug release
cytotoxicity
Content Type
Journal Article
Description
In a previous study, we reported on the development of a synthetic polymer conjugate of pirarubicin (THP) that was formed via an acid-labile hydrazone bond between the polymer and the THP. However, the synthetic polymer itself was non-biodegradable, which could lead to unexpected adverse effects. Human serum albumin (HSA), which has a high biocompatibility and good biodegradability, is also a potent carrier for delivering antitumor drugs. The objective of this study was to develop pH-sensitive HSA conjugates of THP (HSA-THP), and investigate the release of THP and the cytotoxicity under acidic conditions in vitro for further clinical development. HSA-THP was synthesized by conjugating maleimide hydrazone derivatives of THP with poly-thiolated HSA using 2-iminothiolane, via a thiol-maleimide coupling reaction. We synthesized two types of HSA-THP that contained different amounts of THP (HSA-THP2 and HSA-THP4). Free THP was released from both of the HSA conjugates more rapidly at an acidic pH, and the rates of release for HSA-THP2 and HSA-THP4 were similar. Moreover, both HSA-THPs exhibited a higher cytotoxicity at acidic pH than at neutral pH, which is consistent with the effective liberation of free THP under acidic conditions. These findings suggest that these types of HSA-THPs are promising candidates for further development.
Journal Title
Pharmaceuticals
ISSN
14248247
Publisher
MDPI
Volume
14
Issue
1
Start Page
22
Published Date
2020-12-30
Rights
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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DOI (Published Version)
URL ( Publisher's Version )
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language
eng
TextVersion
Publisher
departments
Pharmaceutical Sciences