DELIVERY OF BENZOPORPHYRIN DERIVATIVE, A PHOTOSENSITIZER, INTO ATHEROSCLEROTIC PLAQUE OF WATANABE HERITABLE HYPERLIPIDEMIC RABBITS AND BALLOON-INJURED NEW-ZEALAND RABBITS

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.