Gelatin microspheres encapsulated with a nonpeptide angiogenic agent, ginsenoside Rg1, for intramyocardial injection in a rat model with infarcted myocardium.
Angiogenic therapies may need to select a stable agent to be delivered. In the study, a nonpeptide angiogenic agent, ginsenoside Rg(1) (Rg(1)), was encapsulated in the gelatin microspheres (MSs) crosslinked with genipin and intramuscularly injected into a rat model with infarcted myocardium. bFGF was used as a control. After swelling in an aqueous environment, the MSs without crosslinking became collapsed and stuck together. For those crosslinked, the swollen MSs appeared to be more stable with an increasing the degree of crosslinking. After it was released from MSs in vitro, the remaining activity of bFGF on HUVEC proliferation reduced significantly, while that of Rg(1) remained constant. An inspection of the retrieved hearts revealed a large aneurysmal left ventricle (LV) with a thinned myocardium and a significant myocardial fibrosis for that treated with the Empty MSs (without drug encapsulation). However, those receiving the MSs encapsulated with bFGF or Rg(1) attenuated the enlargement of the LV cavity and the development of myocardial fibrosis. The densities of microvessels found in the border zones of the infarct treated with the bFGF or Rg(1) MSs were significantly greater than that treated with the Empty MSs. These results indicated that Rg(1), a stable angiogenic agent, successfully enhanced the myocardial perfusion and preserved the infarcted LV function.
Wei
Hao-Ji
HJ
Division of Cardiovascular Surgery, Veterans General Hospital-Taichung, and College of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
Yang
Hang-Hsing
HH
Chen
Chun-Hung
CH
Lin
Wei-Wen
WW
Chen
Sung-Ching
SC
Lai
Po-Hong
PH
Chang
Yen
Y
Sung
Hsing-Wen
HW
D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D003326:Coronary Circulation / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000737:chemistry; D004195:Disease Models, Animal; D004337:Drug Carriers; D004339:Drug Compounding; D042783:Endothelial Cells / Q000187:drug effects; D005240:Feasibility Studies; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000737:chemistry; D005355:Fibrosis; D005780:Gelatin / Q000737:chemistry*; D036145:Ginsenosides / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D007273:Injections, Intramuscular; D057889:Iridoid Glycosides; D039823:Iridoids / Q000737:chemistry; D008297:Male; D008863:Microspheres; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects
D043925:Angiogenesis Inducing Agents; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D036145:Ginsenosides; D057889:Iridoid Glycosides; D039823:Iridoids; D016222:Fibroblast Growth Factor 2; D005780:Gelatin; C007834:genipin; C035054:ginsenoside Rg1