Delivery of negatively charged liposomes into the atheromas of Watanabe heritable hyperlipidemic rabbits.
Liposomes have been used as imaging and therapeutic agents in various tissues but only infrequently in the cardiovascular system. We prepared a liposome to target atheromas in a Watanabe heritable hyperlipidemic (WHHL) rabbit model. Liposomes labeled with rhodamine and nanogold were injected intra-arterially into the descending thoracic aortas of WHHL rabbits. The arterial segments of interest were perfusion-fixed and evaluated with immunohistochemistry, light microscopy, and electron microscopy. Deconvolution microscopy showed that rhodamine label was concentrated in the plaque shoulder regions of advanced-stage atheromas; however, rhodamine label was not found in adjacent, non-atherosclerotic aorta. Transmission electron microscopy revealed liposome remnants and the highest concentration of nanogold label in lipid-laden areas of atheromas. Liposomes were concentrated in areas of lipoprotein-associated phospholipase A(2) expression. We conclude that modified liposomes can be delivered to the shoulder regions of advanced atheromas in WHHL rabbits and may be useful therapeutically for targeting metabolically active plaque.
Walton
Brian L
BL
Texas Heart Institute at St Luke's Episcopal Hospital, Houston, TX, USA. BWalton@heart.thi.tmc.edu
Leja
Monika
M
Vickers
Kasey C
KC
Estevez-Fernandez
Monica
M
Sanguino
Angela
A
Wang
Elizabeth
E
Clubb
Fred J
FJ
Morrisett
Joel
J
Lopez-Berestein
Gabriel
G
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D005614:Freeze Fracturing; D006046:Gold / Q000493:pharmacokinetics; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000235:genetics; D007269:Injections, Intra-Arterial; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics*; D053768:Metal Nanoparticles; D008854:Microscopy, Electron; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000235:genetics; D011817:Rabbits; D012235:Rhodamines / Q000493:pharmacokinetics
D008081:Liposomes; D012235:Rhodamines; D006046:Gold; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase