Poly-ion complex formation of heparin and tetrakis (3-aminopropyl) ammonium allows the sustained release of unfractionated heparin
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Authors
Ito, D.
Higashi, K.
Ge, D.
Kogure, N.
Terui, Y.
Linhardt, Robert J.
Toida, T.
Issue Date
2020
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Physical mixtures of cationic polymers and heparin have been developed to overcome the limitations of unfractionated heparin. In this study, we found that heparin associates with natural polyamines in water, resulting in the generation of a poly-ion complex (PIC). PIC formation (or stability) was influenced by the concentration and ratio of heparin and polyamines, molecular weight of heparin, nature of polyamines, and pH conditions. Interestingly, the PIC obtained when heparin and tetrakis (3-aminopropyl) ammonium (Taa) were mixed exhibited stability and was sticky in nature. PIC formation was due to an electrostatic interaction between heparin and Taa. Heparin-Taa PIC was administered subcutaneously to mice, and the time to maximum heparin concentration within the therapeutic range of heparin was markedly increased compared to that after a single dose of heparin. These results suggest that the quaternary ammonium structure of Taa is critical for the preparation of a stable PIC, thereby allowing the sustained release of heparin into the blood.
Description
Heliyon, 6, e05168
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Poly-ion complex formation of heparin and tetrakis (3-aminopropyl) ammonium allows the sustained release of unfractionated heparin, D. Ito, K. Higashi, D. Ge, N. Kogure, Y. Terui, R. J. Linhardt, T. Toida, Heliyon, 6, e05168, 2020.
Publisher
Elsevier