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

Biomedical engineering Biotechnology Materials application Materials characterization Pharmaceutical science Poly-ion complex Polyamine Sustained release of heparin

Journal

Heliyon
ISSN: 2405-8440
Titre abrégé: Heliyon
Pays: England
ID NLM: 101672560

Informations de publication

Date de publication:
Oct 2020
Historique:
received: 09 05 2020
revised: 04 08 2020
accepted: 01 10 2020
entrez: 12 10 2020
pubmed: 13 10 2020
medline: 13 10 2020
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 33043161
doi: 10.1016/j.heliyon.2020.e05168
pii: S2405-8440(20)32011-9
pmc: PMC7538075
doi:

Types de publication

Journal Article

Langues

eng

Pagination

e05168

Informations de copyright

© 2020 The Author(s).

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Auteurs

Daichi Ito (D)

Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.

Dan Ge (D)

Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.

Noriyuki Kogure (N)

Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.

Hitomi Manaka (H)

Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.

Yusuke Terui (Y)

Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomi-cho, Choshi, Chiba 288-0025, Japan.

Hiromitsu Takayama (H)

Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.

Robert J Linhardt (RJ)

Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 121806, United States.

Toshihiko Toida (T)

Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.

Kyohei Higashi (K)

Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.

Classifications MeSH