Increased accumulation of PEG-PE micelles in the area of experimental myocardial infarction in rabbits.
Micelles prepared from polyethyleneglycol/phosphatidyl-ethanolamine conjugates (PEG-PE) with a size of 7-20 nm and zeta-potential of approximately -18 mV were administered i.v. to rabbits with experimental myocardial infarctions. Micelles demonstrated a prolonged circulation in the blood (half-life of 2 h) and accumulated in the infarction zone with efficiency more than 8-fold higher as compared to a non-damaged part of the heart muscle. Obtained results suggest that the enhanced permeability and retention (EPR) effect is the primary mechanism of accumulation of microparticles in the infarct areas, and that drug carriers such as PEG-PE micelles can be used for the delivery of therapeutic or diagnostic agents to an area of myocardial infarction.
Lukyanov
Anatoly N
AN
Department of Pharmaceutical Sciences, Bouve College of Health Sciences, Northeastern University, 360 Huntington Avenue, 312 Mugar Building, Boston, MA 02115, USA.
Hartner
William C
WC
Torchilin
Vladimir P
VP
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000378:metabolism; D004195:Disease Models, Animal; D004562:Electrocardiography / Q000187:drug effects / Q000379:methods; D008297:Male; D008823:Micelles; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism*; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits
D008823:Micelles; D010714:Phosphatidylethanolamines; C067972:dioleoyl-N-(monomethoxypolyethylene glycol succinyl)phosphatidylethanolamine; D011092:Polyethylene Glycols