Photodynamic therapy for corneal neovascularization using polymeric micelles encapsulating dendrimer porphyrins

PURPOSE: To investigate the accumulation of new photosensitizers (PSs), dendrimer porphyrin (DP, free DP), and DP encapsulation into polymeric micelles (DP-micelle) and the efficacy of photodynamic therapy (PDT) in an experimental corneal neovascularization model in mice. METHODS: Corneal neovascularization was induced by suturing 10-0 nylon 1 mm away from the limbal vessel in C57BL6/J mice. To determine the accumulation of free DP and DP-micelle, 10 mg/kg free DP or DP-micelle was administered by intravenous injection 4 days after suture placement. Mice were killed 1, 4, 24, and 168 hours after the injection of PS. Twenty-four hours after the administration of free DP or DP-micelle, mice were treated with a diode laser of 438-nm wavelength at 10 or 50 J/cm(2). Fluorescein angiography was performed before and 7 days after irradiation, and the area of corneal neovascularization was quantified. RESULTS: Free DP and DP-micelle accumulated in the neovascularized area 1 hour to 24 hours after administration. Fluorescence of DP was weaker than that of DP-micelle. Neither DP-micelle nor DP could be detected in normal limbal vasculature. In the PDT experiments using PS, mean residual rates of corneal neovascularization were 10.1% in the mice treated with DP-micelle and 21.6% in the mice treated with free DP at 10 J/cm(2) (P < 0.01). At 50 J/cm(2), mean residual rates of corneal neovascularization were 10.6% in the mice treated with DP-micelle and 13.7% in the mice treated with free DP (P > 0.05). Although corneal neovascularization in PDT-treated mice exhibited significant regression compared with the control group, significant energy-related vessel regression with increasing laser energy could not be observed. CONCLUSIONS: PDT with DP-micelle and free DP can provide efficacious treatment of corneal neovascularization.