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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| Format: | Article |
| Language: | English |
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Elsevier
2020-10-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844020320119 |
| _version_ | 1819198898658344960 |
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| author | Daichi Ito Dan Ge Noriyuki Kogure Hitomi Manaka Yusuke Terui Hiromitsu Takayama Robert J. Linhardt Toshihiko Toida Kyohei Higashi |
| author_facet | Daichi Ito Dan Ge Noriyuki Kogure Hitomi Manaka Yusuke Terui Hiromitsu Takayama Robert J. Linhardt Toshihiko Toida Kyohei Higashi |
| author_sort | Daichi Ito |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T03:07:46Z |
| format | Article |
| id | doaj.art-812c12e1abe74ff3970ea6d46b5bbe0b |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-12-23T03:07:46Z |
| publishDate | 2020-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-812c12e1abe74ff3970ea6d46b5bbe0b2022-12-21T18:02:17ZengElsevierHeliyon2405-84402020-10-01610e05168Poly-ion complex (PIC) formation of heparin and polyamines: PIC with tetrakis (3-aminopropyl) ammonium allows sustained release of heparinDaichi Ito0Dan Ge1Noriyuki Kogure2Hitomi Manaka3Yusuke Terui4Hiromitsu Takayama5Robert J. Linhardt6Toshihiko Toida7Kyohei Higashi8Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, JapanGraduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, JapanGraduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, JapanFaculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, JapanFaculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomi-cho, Choshi, Chiba 288-0025, JapanGraduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, JapanCenter for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 121806, United StatesGraduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, JapanFaculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2405844020320119Poly-ion complexPolyamineSustained release of heparinMaterials applicationMaterials characterizationBiotechnology |
| spellingShingle | Daichi Ito Dan Ge Noriyuki Kogure Hitomi Manaka Yusuke Terui Hiromitsu Takayama Robert J. Linhardt Toshihiko Toida Kyohei Higashi Poly-ion complex (PIC) formation of heparin and polyamines: PIC with tetrakis (3-aminopropyl) ammonium allows sustained release of heparin Heliyon Poly-ion complex Polyamine Sustained release of heparin Materials application Materials characterization Biotechnology |
| title | Poly-ion complex (PIC) formation of heparin and polyamines: PIC with tetrakis (3-aminopropyl) ammonium allows sustained release of heparin |
| title_full | Poly-ion complex (PIC) formation of heparin and polyamines: PIC with tetrakis (3-aminopropyl) ammonium allows sustained release of heparin |
| title_fullStr | Poly-ion complex (PIC) formation of heparin and polyamines: PIC with tetrakis (3-aminopropyl) ammonium allows sustained release of heparin |
| title_full_unstemmed | Poly-ion complex (PIC) formation of heparin and polyamines: PIC with tetrakis (3-aminopropyl) ammonium allows sustained release of heparin |
| title_short | Poly-ion complex (PIC) formation of heparin and polyamines: PIC with tetrakis (3-aminopropyl) ammonium allows sustained release of heparin |
| title_sort | poly ion complex pic formation of heparin and polyamines pic with tetrakis 3 aminopropyl ammonium allows sustained release of heparin |
| topic | Poly-ion complex Polyamine Sustained release of heparin Materials application Materials characterization Biotechnology |
| url | http://www.sciencedirect.com/science/article/pii/S2405844020320119 |
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