DELIVERY OF BENZOPORPHYRIN DERIVATIVE, A PHOTOSENSITIZER, INTO ATHEROSCLEROTIC PLAQUE OF WATANABE HERITABLE HYPERLIPIDEMIC RABBITS AND BALLOON-INJURED NEW-ZEALAND RABBITS
Ba. Allison et al., DELIVERY OF BENZOPORPHYRIN DERIVATIVE, A PHOTOSENSITIZER, INTO ATHEROSCLEROTIC PLAQUE OF WATANABE HERITABLE HYPERLIPIDEMIC RABBITS AND BALLOON-INJURED NEW-ZEALAND RABBITS, Photochemistry and photobiology, 65(5), 1997, pp. 877-883
In this study we compared the plasma distribution and arterial accumul
ation of a photosensitizer, benzoporphyrin derivative (BPD), in two mo
dels of atherosclerosis: the spontaneous lesions of the Watanabe herit
able hyperlipidemic (WHHL) rabbit and induced lesions of the balloon-i
njured, cholesterol-fed New Zealand white (NZW) rabbit. Selective upta
ke and retention of a photosensitizer by the abnormal portion of a ves
sel is a necessity in order for photodynamic therapy to become a succe
ssful modality for inhibition of intimal hyperplasia, selective remova
l of atherosclerotic tissue or imaging of diseased arteries, Liposome-
based formulations were compared to freshly isolated native low densit
y lipoprotein (LDL) and acetylated-LDL (Ac-LDL) as delivery vehicles f
or BPD, Plasma distribution of the photosensitizer was analyzed by KBr
density gradient ultracentrifugation, Although the delivery vehicle i
nfluenced plasma distribution immediately postinjection, BPD subsequen
tly partitioned according to the plasma concentration of the lipoprote
ins. Photosensitizer level in plaque and normal artery specimens was d
etermined by ethyl acetate extraction and spectrofluorometric measurem
ent. The measurement of BPD in normal and atherosclerotic arterial tis
sue demonstrated a selective accumulation in atherosclerotic tissue, P
reassociation with LDL and Ac-LDL enhanced accumulation of BPD in athe
rosclerotic tissue when compared with normal artery (mean ratios of 2.
8 and 4.1 were achieved, respectively), These results indicate that th
e preferential uptake of BPD by atherosclerotic plaque can be enhanced
by preassociation with plasma lipoproteins, suggesting that light act
ivation could lead to a highly selective destruction of diseased vascu
lar tissue.