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In vivo uptake of liposomal benzoporphyrin derivative and photothrombosis in experimental corneal neovascularization
Authors:Ursula Schmidt-Erfurth  Tayyaba Hasan  Kevin Schomacker  Thomas Flotte  Reginald Birngruber
Abstract:Background and Objective: Photodynamic therapy (PDT) has been used successfully to occlude neovascularizations experimentally. We evaluated the vasoocclusive potential of benzoporphyrin derivative (BPD), a new photosensitizer currently in clinical trials. Since liposomally formulated BPD strongly binds to endogenous low density lipoproteins (LDL) after i.v. injection, LDL act as carrier to deliver BPD preferentially to proliferating endothelial cells. Study Design/Materials and Methods: Corneal neovascularizations in rabbits were used as model. Time-dependent uptake and retention of liposomal BPD were measured in vivo by monitoring the laser-induced fluorescence (LIF). Photothrombosis was induced using a dye laser emitting at 692 nm. Results: A maximal BPD concentration was measured at 60–90 minutes postinjection determining the optimal time interval for treatment. Exposures as low as 10 J/cm2 allowed complete and irreversible neovascular occlusion as documented angiographically. Histology revealed selective endothelial damage, adjacent corneal stroma, or iris vessels, remained intact. Identical results were obtained using BPD directly complexed with LDL suggesting use of a LDL-mediated pathway. Conclusion: We suggest BPD-PDT for a selective treatment of neovascular diseases. © 1995 Wiley-Liss, Inc.
Keywords:benzoporphyrin derivative  ocular photothrombosis  liposomes  cornea  neovascularization
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