Poly-ion complex (PIC) formation of heparin and polyamines: PIC with tetrakis (3-aminopropyl) ammonium allows sustained release of heparin

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 in...

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Bibliographic Details
Published in:Heliyon 2020-10, Vol.6 (10), p.e05168-e05168, Article e05168
Main Authors: Ito, Daichi, Ge, Dan, Kogure, Noriyuki, Manaka, Hitomi, Terui, Yusuke, Takayama, Hiromitsu, Linhardt, Robert J., Toida, Toshihiko, Higashi, Kyohei
Format: Article
Language:English
Subjects:
ammonium
Biomedical engineering
Biotechnology
blood
electrostatic interactions
heparin
Materials application
Materials characterization
molecular weight
Pharmaceutical science
Poly-ion complex
Polyamine
polyamines
quaternary ammonium compounds
Sustained release of heparin
therapeutics
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Summary: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. Poly-ion complex; Polyamine; Sustained release of heparin; Materials application; Materials characterization; Biotechnology; Pharmaceutical science; Biomedical engineering
ISSN:2405-8440
2405-8440
DOI:10.1016/j.heliyon.2020.e05168