Effective transscleral delivery of two retinal anti-angiogenic molecules: carboxyamido-triazole (CAI) and 2-methoxyestradiol (2ME2).
OBJECTIVE
To evaluate the human transscleral diffusion and intravitreal delivery of carboxyamido-triazole (CAI) and 2-Methoxyestradiol (2ME2).


METHODS
The transscleral diffusion of two retinal antiangiogenic molecules, CAI and 2ME2, was measured in vitro to assess their potential transscleral delivery. Varying concentrations and different solvents of CAI and 2ME2 were placed in the upper compartment of a two-chamber acrylic perfusion apparatus, on the episcleral side of the sclera obtained from human donor eyes. Samples were taken from the lower compartment (uveal side) for up to 24 hours and measured by high performance liquid chromatography.


RESULTS
All three solutions that contained CAI efficiently diffused through the sclera with permeability constants that ranged from 2.8 to 5.5 x 10 cm/s. The scleral permeability constant derived for 2ME2 was 9.96 x 10 cm/s. The permeability constants obtained for both CAI and 2ME2 are similar to each other as well as to permeability constants measured for other small molecules such as fluorescein and dexamethasone fluorescein.


CONCLUSIONS
Both CAI and 2ME2 traverse the sclera efficiently. These data combined with the reported inhibition of posterior segment neovascularization observed with these two molecules demonstrates that CAI and 2ME2 are good candidate molecules to treat posterior segment neovascularization by local delivery.
Cruysberg
Lars P J
LP
Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Franklin
Alan J
AJ
Sanders
Jason
J
Self
Cindy
C
Yuan
Peng
P
Csaky
Karl G
KG
Robinson
Michael R
MR
Kohn
Elise C
EC
Edelhauser
Henry F
HF
D000077584:2-Methoxyestradiol; D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics*; D001692:Biological Transport; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D015194:Diffusion Chambers, Culture; D016503:Drug Delivery Systems; D004958:Estradiol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D008875:Middle Aged; D010539:Permeability; D012590:Sclera / Q000378:metabolism* / Q000648:ultrastructure; D014019:Tissue Donors; D014230:Triazoles / Q000493:pharmacokinetics*
D020533:Angiogenesis Inhibitors; D014230:Triazoles; D004958:Estradiol; D000077584:2-Methoxyestradiol; C062058:carboxyamido-triazole