Photodynamic Therapy for Corneal Neovascularization Using Polymeric Micelles Encapsulating Dendrimer Porphyrins

Kenji Sugisaki, Tomohiko Usui, Nobuhiro Nishiyama, Woo-Dong Jang, Yasuo Yanagi, Satoru Yamagami, Shiro Amano, Kazunori Kataoka
2008 Investigative Ophthalmology and Visual Science  
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 DPmicelle, 10 mg/kg free DP or DP-micelle was administered
more » ... by intravenous injection 4 days after suture placement. Mice were killed 1, 4, 24, and 168 hours after the injection of PS. Twentyfour 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 Ͻ 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 Ͼ 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. (Invest Ophthalmol Vis Sci. 2008;49:894 -899)
doi:10.1167/iovs.07-0389 pmid:18326709 fatcat:p3wri6t4ebde7mijbhctllc4ja