Angiostatic steroids potentiated by sulfated cyclodextrins inhibit corneal neovascularization.
It is known that hydrocortisone can be converted to a potent angiogenesis inhibitor by coadministration with heparin or with a sulfated cyclodextrin. The activity of tetrahydrocortisol-S, a purely angiostatic corticosteroid, can be potentiated by beta-cyclodextrin tetradecasulfate as shown in this study. This drug "pair" and other pairs of corticosteroids and beta-cyclodextrin tetradecasulfate can be applied topically to inhibit corneal neovascularization. Endotoxin-induced corneal neovascularization in rabbits was treated with beta-cyclodextrin tetradecasulfate coadministered with either: hydrocortisone, tetrahydrocortisol-S, or 6-alpha-fluoro-17,21-dihydroxy-16-beta-methyl-pregna-4,9(11),diene,3, 20-dione. When optimal ratios of steroid and cyclodextrin were used, neovascularization was reduced to 13%, 26%, and 28% of untreated controls for the three steroids, respectively. Hydrocortisone-cyclodextrin drug pairs suppressed virtually all inflammatory cell infiltration (induced by endotoxin), whereas tetrahydrocortisol-cyclodextrin pairs only partially reduced inflammation. These results demonstrate that corneal neovascularization and corneal inflammation are separable processes and that the neovascularization may be treated specifically using angiostatic steroids without inflammatory activity.
Li
W W
WW
Department of Surgery, Children's Hospital, Boston, MA 02115.
Casey
R
R
Gonzalez
E M
EM
Folkman
J
J
D000287:Administration, Topical; D043925:Angiogenesis Inducing Agents / Q000037:antagonists & inhibitors*; D000818:Animals; D001623:Betamethasone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016510:Corneal Neovascularization / Q000473:pathology / Q000517:prevention & control*; D003350:Cortodoxone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003505:Cyclodextrins / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004357:Drug Synergism; D006854:Hydrocortisone / Q000627:therapeutic use*; D008297:Male; D011817:Rabbits; D047392:beta-Cyclodextrins
D043925:Angiogenesis Inducing Agents; D003505:Cyclodextrins; D047392:beta-Cyclodextrins; C064089:beta-cyclodextrin tetradecasulfate; C071297:U 72745G; C009412:tetrahydro-11-deoxycortisol; D001623:Betamethasone; D003350:Cortodoxone; D006854:Hydrocortisone