In vivo hypertensive arterial wall uptake of radiolabeled liposomes.
Using five sham-operated and seven aortic coarctation-induced hypertensive New Zealand White rabbits intravenously injected with neutral small unilamellar vesicles loaded with [111In]nitrilotriacetic acid, we demonstrated in vivo that the normal aortic arterial wall participates in liposome uptake and that this uptake is increased in the hypertensive aortic wall by approximately threefold (p less than or equal to 0.0001). Among the three regions examined, aortic arch, thoracic aorta, and lower abdominal aorta, the difference in uptake between the normotensive and hypertensive arterial walls was significantly different, p less than or equal to 0.05, p less than or equal to 0.0001, and p less than 0.05, respectively. The uptake by the different regions of the hypertensive arterial wall is consistent with the pathological changes present in these areas. Furthermore, the extent of liposome uptake by the aortic wall is strongly correlated with the height of the blood pressure (r = 0.85, p = 0.001, n = 11). We conclude that neutral small unilamellar liposomes can be used to carry agents into the arterial wall in vivo in the study of hypertensive vascular disease and could be especially useful for the delivery of pharmacologically or biologically active agents that would otherwise be inactivated within the circulation or are impermeable to the arterial wall.
Hodis
H N
HN
Department of Internal Medicine, University of Southern California School of Medicine, Los Angeles 90033.
Amartey
J K
JK
Crawford
D W
DW
Wickham
E
E
Blankenhorn
D H
DH
D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001794:Blood Pressure; D004337:Drug Carriers; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D007205:Indium Radioisotopes; D008081:Liposomes / Q000378:metabolism*; D008297:Male; D011817:Rabbits
D004337:Drug Carriers; D007205:Indium Radioisotopes; D008081:Liposomes