Photodynamic therapy for corneal neovascularization using polymeric micelles encapsulating dendrimer porphyrins.
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.
Sugisaki
Kenji
K
Department of Ophthalmology, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Japan
Usui
Tomohiko
T
Nishiyama
Nobuhiro
N
Jang
Woo-Dong
WD
Yanagi
Yasuo
Y
Yamagami
Satoru
S
Amano
Shiro
S
Kataoka
Kazunori
K
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
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