Preparation and characterization of low-molecular-weight heparin/protamine nanoparticles (LMW-H/P NPs) as FGF-2 carrier
Yasutaka Mori1,3,4, Shingo Nakamura2, Satoko Kishimoto1, Mitsuyuki Kawakami4, Satoshi Suzuki4, Takemi Matsui4, Masayuki Ishihara11Research Institute, 2Department of Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan; 3Aeromedical Laboratory, Japan Air Self-Defense Force, Sayama, S...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2010-03-01
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| Series: | International Journal of Nanomedicine |
| Online Access: | http://www.dovepress.com/preparation-and-characterization-of-low-molecular-weight-heparinprotam-a4078 |
| _version_ | 1818909600963887104 |
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| author | Yasutaka Mori Shingo Nakamura Satoko Kishimoto et al |
| author_facet | Yasutaka Mori Shingo Nakamura Satoko Kishimoto et al |
| author_sort | Yasutaka Mori |
| collection | DOAJ |
| description | Yasutaka Mori1,3,4, Shingo Nakamura2, Satoko Kishimoto1, Mitsuyuki Kawakami4, Satoshi Suzuki4, Takemi Matsui4, Masayuki Ishihara11Research Institute, 2Department of Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan; 3Aeromedical Laboratory, Japan Air Self-Defense Force, Sayama, Saitama, Japan; 4Faculty of System Design, Tokyo Metropolitan University, Hino, Tokyo, JapanAbstract: We produced low-molecular-weight heparin/protamine nanoparticles (LMW-H/P NPs) as a carrier for heparin-binding growth factors, such as fibroblast growth factor-2 (FGF-2). A mixture of low-molecular-weight heparin (MW: about 5000 Da, 6.4 mg/mL) and protamine (MW: about 3000 Da, 10 mg/mL) at a ratio of 7:3 (vol:vol) yields a dispersion of microparticles (1–6 μm in diameter). In this study, diluted low-molecular-weight heparin solution in saline (0.32 mg/mL) mixed with diluted protamine (0.5 mg/mL) at a ratio at 7:3 (vol:vol) resulted in soluble nanoparticles (112.5 ± 46.1 nm in diameter). The generated NPs could be then stabilized by adding 2 mg/mL dextran (MW: 178-217 kDa) and remained soluble after lyophilization of dialyzed LMW-H/P NP solution. We then evaluated the capacity of LMW-H/P NPs to protect activity of FGF-2. Interaction between FGF-2 and LMW-H/P NPs substantially prolonged the biological half-life of FGF-2. Furthermore, FGF-2 molecules were protected from inactivation by heat and proteolysis in the presence of LMW-H/P NPs.Keywords: polyelectrolyte complexes, nanoparticles, fibroblast growth factor-2, drug carrier |
| first_indexed | 2024-12-19T22:29:30Z |
| format | Article |
| id | doaj.art-fd16341a8df241ad99b294d80fed92bc |
| institution | Directory Open Access Journal |
| issn | 1176-9114 1178-2013 |
| language | English |
| last_indexed | 2024-12-19T22:29:30Z |
| publishDate | 2010-03-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-fd16341a8df241ad99b294d80fed92bc2022-12-21T20:03:23ZengDove Medical PressInternational Journal of Nanomedicine1176-91141178-20132010-03-012010default147155Preparation and characterization of low-molecular-weight heparin/protamine nanoparticles (LMW-H/P NPs) as FGF-2 carrierYasutaka MoriShingo NakamuraSatoko Kishimotoet alYasutaka Mori1,3,4, Shingo Nakamura2, Satoko Kishimoto1, Mitsuyuki Kawakami4, Satoshi Suzuki4, Takemi Matsui4, Masayuki Ishihara11Research Institute, 2Department of Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan; 3Aeromedical Laboratory, Japan Air Self-Defense Force, Sayama, Saitama, Japan; 4Faculty of System Design, Tokyo Metropolitan University, Hino, Tokyo, JapanAbstract: We produced low-molecular-weight heparin/protamine nanoparticles (LMW-H/P NPs) as a carrier for heparin-binding growth factors, such as fibroblast growth factor-2 (FGF-2). A mixture of low-molecular-weight heparin (MW: about 5000 Da, 6.4 mg/mL) and protamine (MW: about 3000 Da, 10 mg/mL) at a ratio of 7:3 (vol:vol) yields a dispersion of microparticles (1–6 μm in diameter). In this study, diluted low-molecular-weight heparin solution in saline (0.32 mg/mL) mixed with diluted protamine (0.5 mg/mL) at a ratio at 7:3 (vol:vol) resulted in soluble nanoparticles (112.5 ± 46.1 nm in diameter). The generated NPs could be then stabilized by adding 2 mg/mL dextran (MW: 178-217 kDa) and remained soluble after lyophilization of dialyzed LMW-H/P NP solution. We then evaluated the capacity of LMW-H/P NPs to protect activity of FGF-2. Interaction between FGF-2 and LMW-H/P NPs substantially prolonged the biological half-life of FGF-2. Furthermore, FGF-2 molecules were protected from inactivation by heat and proteolysis in the presence of LMW-H/P NPs.Keywords: polyelectrolyte complexes, nanoparticles, fibroblast growth factor-2, drug carrierhttp://www.dovepress.com/preparation-and-characterization-of-low-molecular-weight-heparinprotam-a4078 |
| spellingShingle | Yasutaka Mori Shingo Nakamura Satoko Kishimoto et al Preparation and characterization of low-molecular-weight heparin/protamine nanoparticles (LMW-H/P NPs) as FGF-2 carrier International Journal of Nanomedicine |
| title | Preparation and characterization of low-molecular-weight heparin/protamine nanoparticles (LMW-H/P NPs) as FGF-2 carrier |
| title_full | Preparation and characterization of low-molecular-weight heparin/protamine nanoparticles (LMW-H/P NPs) as FGF-2 carrier |
| title_fullStr | Preparation and characterization of low-molecular-weight heparin/protamine nanoparticles (LMW-H/P NPs) as FGF-2 carrier |
| title_full_unstemmed | Preparation and characterization of low-molecular-weight heparin/protamine nanoparticles (LMW-H/P NPs) as FGF-2 carrier |
| title_short | Preparation and characterization of low-molecular-weight heparin/protamine nanoparticles (LMW-H/P NPs) as FGF-2 carrier |
| title_sort | preparation and characterization of low molecular weight heparin protamine nanoparticles lmw h p nps as fgf 2 carrier |
| url | http://www.dovepress.com/preparation-and-characterization-of-low-molecular-weight-heparinprotam-a4078 |
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