Abstract
The clinical efficacy of hepatocyte growth factor (HGF) in tissue repair can be greatly enhanced by high affinity, biocompatible drug carriers that maintain the bioactivity and regulate release at the target site. We produced 0.5-3.0 μm fragmin (low molecular weight heparin)/protamine microparticles (F/P MPs) as carriers for the controlled release of HGF. F/P MPs immobilized more than 3 μg of HGF per mg of MPs and gradually released the absorbed HGF into the medium with a half-release time of approximately 5 days. Compared with HGF alone, HGF-containing F/P MPs substantially enhanced the mitogenic effect of HGF on cultured human microvascular endothelial cells, by prolonging the biological half-life, and its conjugation to F/P MPs protected HGF from heat and proteolytic inactivation. F/P MPs disappeared 8 days after subcutaneous injection in mice, suggesting that they are rapidly biodegraded. Furthermore, the number of large (diameter ≥200 μm or containing ≥100 erythrocytes) and medium (diameter 20-200 μm or containing 10-100 erythrocytes) lumen capillaries 8 days after injection of HGF-containing F/P MPs was significantly higher than that after injection of HGF or F/P MPs alone. Furthermore, the number of small (diameter ≤20 μm or containing 1-10 erythrocytes) lumen capillaries was significantly higher 4 days after injection of HGF-containing F/P MPs. This increased angiogenic activity of HGF in vivo is probably due to both sustained local release and protection against biodegradation by the F/P MPs. Thus, F/P MPs may be useful and safe HGF carriers that facilitate cell proliferation and vascularization at sites of tissue damage.
| Original language | English |
|---|---|
| Pages (from-to) | 4763-4770 |
| Number of pages | 8 |
| Journal | Acta Biomaterialia |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2013 Jan |
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Keywords
- Angiogenesis
- Drug carrier
- Hepatocyte growth factor
- Low molecular weight heparin (fragmin)/protamine microparticles
ASJC Scopus subject areas
- Biomaterials
- Biomedical Engineering
- Biotechnology
- Biochemistry
- Molecular Biology
Cite this
Fragmin/protamine microparticles to adsorb and protect HGF and to function as local HGF carriers in vivo. / Kishimoto, Satoko; Ishihara, Masayuki; Nakamura, Shingo; Fujita, Masanori; Takikawa, Megumi; Sumi, Yuki; Kiyosawa, Tomoharu; Sato, Toshinori; Kanatani, Yasuhiro.
In: Acta Biomaterialia, Vol. 9, No. 1, 01.2013, p. 4763-4770.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Fragmin/protamine microparticles to adsorb and protect HGF and to function as local HGF carriers in vivo
AU - Kishimoto, Satoko
AU - Ishihara, Masayuki
AU - Nakamura, Shingo
AU - Fujita, Masanori
AU - Takikawa, Megumi
AU - Sumi, Yuki
AU - Kiyosawa, Tomoharu
AU - Sato, Toshinori
AU - Kanatani, Yasuhiro
PY - 2013/1
Y1 - 2013/1
N2 - The clinical efficacy of hepatocyte growth factor (HGF) in tissue repair can be greatly enhanced by high affinity, biocompatible drug carriers that maintain the bioactivity and regulate release at the target site. We produced 0.5-3.0 μm fragmin (low molecular weight heparin)/protamine microparticles (F/P MPs) as carriers for the controlled release of HGF. F/P MPs immobilized more than 3 μg of HGF per mg of MPs and gradually released the absorbed HGF into the medium with a half-release time of approximately 5 days. Compared with HGF alone, HGF-containing F/P MPs substantially enhanced the mitogenic effect of HGF on cultured human microvascular endothelial cells, by prolonging the biological half-life, and its conjugation to F/P MPs protected HGF from heat and proteolytic inactivation. F/P MPs disappeared 8 days after subcutaneous injection in mice, suggesting that they are rapidly biodegraded. Furthermore, the number of large (diameter ≥200 μm or containing ≥100 erythrocytes) and medium (diameter 20-200 μm or containing 10-100 erythrocytes) lumen capillaries 8 days after injection of HGF-containing F/P MPs was significantly higher than that after injection of HGF or F/P MPs alone. Furthermore, the number of small (diameter ≤20 μm or containing 1-10 erythrocytes) lumen capillaries was significantly higher 4 days after injection of HGF-containing F/P MPs. This increased angiogenic activity of HGF in vivo is probably due to both sustained local release and protection against biodegradation by the F/P MPs. Thus, F/P MPs may be useful and safe HGF carriers that facilitate cell proliferation and vascularization at sites of tissue damage.
AB - The clinical efficacy of hepatocyte growth factor (HGF) in tissue repair can be greatly enhanced by high affinity, biocompatible drug carriers that maintain the bioactivity and regulate release at the target site. We produced 0.5-3.0 μm fragmin (low molecular weight heparin)/protamine microparticles (F/P MPs) as carriers for the controlled release of HGF. F/P MPs immobilized more than 3 μg of HGF per mg of MPs and gradually released the absorbed HGF into the medium with a half-release time of approximately 5 days. Compared with HGF alone, HGF-containing F/P MPs substantially enhanced the mitogenic effect of HGF on cultured human microvascular endothelial cells, by prolonging the biological half-life, and its conjugation to F/P MPs protected HGF from heat and proteolytic inactivation. F/P MPs disappeared 8 days after subcutaneous injection in mice, suggesting that they are rapidly biodegraded. Furthermore, the number of large (diameter ≥200 μm or containing ≥100 erythrocytes) and medium (diameter 20-200 μm or containing 10-100 erythrocytes) lumen capillaries 8 days after injection of HGF-containing F/P MPs was significantly higher than that after injection of HGF or F/P MPs alone. Furthermore, the number of small (diameter ≤20 μm or containing 1-10 erythrocytes) lumen capillaries was significantly higher 4 days after injection of HGF-containing F/P MPs. This increased angiogenic activity of HGF in vivo is probably due to both sustained local release and protection against biodegradation by the F/P MPs. Thus, F/P MPs may be useful and safe HGF carriers that facilitate cell proliferation and vascularization at sites of tissue damage.
KW - Angiogenesis
KW - Drug carrier
KW - Hepatocyte growth factor
KW - Low molecular weight heparin (fragmin)/protamine microparticles
UR - http://www.scopus.com/inward/record.url?scp=84870241115&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84870241115&partnerID=8YFLogxK
U2 - 10.1016/j.actbio.2012.08.003
DO - 10.1016/j.actbio.2012.08.003
M3 - Article
C2 - 22935325
AN - SCOPUS:84870241115
VL - 9
SP - 4763
EP - 4770
JO - Acta Biomaterialia
JF - Acta Biomaterialia
SN - 1742-7061
IS - 1
ER -