title: Photodynamic therapy for corneal neovascularization using polymeric micelles encapsulating dendrimer porphyrins.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Japan
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugisaki
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Usui
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishiyama
authors.forename: Woo-Dong
authors.initials: WD
authors.lastname: Jang
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yanagi
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamagami
authors.forename: Shiro
authors.initials: S
authors.lastname: Amano
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
mesh_terms: D000818:Animals; D016510:Corneal Neovascularization / Q000188:drug therapy*; D050091:Dendrimers; D004195:Disease Models, Animal; D004337:Drug Carriers; D016650:Fluorescein-5-isothiocyanate; D008297:Male; D008665:Metalloporphyrins / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D008823:Micelles; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011092:Polyethylene Glycols; D011107:Polylysine
chemical_list: C099578:(O-methylpoly(ethylene glycol)-O'-succinyl)-N-epsilon-poly(L-lysine); D050091:Dendrimers; D004337:Drug Carriers; D008665:Metalloporphyrins; D008823:Micelles; D017319:Photosensitizing Agents; C017802:zinc hematoporphyrin; D011107:Polylysine; D011092:Polyethylene Glycols; D016650:Fluorescein-5-isothiocyanate