Targeted delivery of antibody conjugated liposomal drug carriers to rat myocardial infarction

• Published in: Biotechnology and bioengineering 2007-03, Vol.96 (4), p.795-802
• Main Authors: Scott, Robert C., Wang, Bin, Nallamothu, RamaKrishna, Pattillo, Christopher B., Perez-Liz, Georgina, Issekutz, Andrew, Valle, Luis Del, Wood, George C., Kiani, Mohammad F.
• Format: Article
• Language: English
• Subjects: adhesion molecules; Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - immunology; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - immunology; Biological and medical sciences; Biotechnology; Cell adhesion & migration; Disease Models, Animal; Drug Carriers - chemical synthesis; Drug Carriers - pharmacology; Drug therapy; Fundamental and applied biological sciences. Psychology; Heart attacks; Immunoglobulins; Inflammation - drug therapy; Liposomes; Male; myocardial infarction; Myocardial Infarction - drug therapy; Myocardium - immunology; Myocardium - pathology; P-selectin; P-Selectin - immunology; Rats; Rats, Sprague-Dawley; Rodents; targeted drug delivery
• ISSN: 0006-3592; 1097-0290
• DOI: 10.1002/bit.21233

Immunoliposome (IL) targeting to areas of inflammation after an acute myocardial infarction (MI) could provide the means by which pro‐angiogenic compounds can be selectively targeted to the infarcted region. The adhesion of model drug carriers and ILs coated with an antibody to P‐selectin was quantified in a rat model of MI following left coronary artery ligation. Anti‐P‐selectin coated model drug carriers showed a 140% and 180% increase in adhesion in the border zone of the MI 1 and 4 h post‐MI, respectively. Radiolabeled anti‐P‐selectin ILs injected immediately post‐MI and allowed to circulate 24 h showed an 83% increase in targeting to infarcted myocardium when compared to adjacent non‐infarcted myocardium. Radiolabeled anti‐P‐selectin ILs injected 4 h post‐MI and allowed to circulate for 24 h showed a 92% increase in accumulation in infarcted myocardium when compared to adjacent non‐infarcted myocardium. Targeting to upregulated adhesion molecules on the endothelium provides a promising strategy for selectively delivering compounds to the infarct region of the myocardium using our liposomal‐based drug delivery vehicle. Biotechnol. Bioeng. 2007;96:795–802. © 2006 Wiley Periodicals, Inc.