The effect of angiostatic steroids and beta-cyclodextrin tetradecasulfate on corneal neovascularization in the rat.
Folkman and coworkers have described angiostatic steroids that markedly inhibit neovascularization of the rabbit cornea when given topically with beta-cyclodextrin tetradecasulfate (beta-CD), yet have minimal or no glucocorticoid or mineralocorticoid activity. Our objective was to extend these observations to another species, the rat. We induced neovascularization by cauterizing rat corneas with silver nitrate/potassium nitrate; drugs were applied topically four times per day for 4 days in most experiments. Submicron sized emulsions of lipid-soluble dexamethasone and the angiostatic steroids 17 alpha-hydroxyprogesterone (1 or 10 mg ml-1) and cortexolone (1 or 10 mg ml-1) were prepared by lecithin encapsulation of drug microcrystals. The vehicle for water-soluble hydrocortisone 21-phosphate (HCP) +/- beta-CD (Molecusol; Pharmatec, Inc) was 10% Tween 20 in Tris-buffered 0.9% saline. Angiogenesis was significantly inhibited only by 1 mg ml-1 dexamethasone (-63.2% when compared with controls), 0.5 mg ml-1 HCP + 1 mg ml-1 beta-CD (-33.4%), and 1 mg ml-1 HCP (-40.2%). HCP (0.5 mg ml-1) or beta-CD (1 or 2 mg ml-1) alone had no significant effect on neovascularization; the inhibition by 1.0 mg ml-1 HCP was not potentiated by 2 mg ml-1 beta-CD. We also tested HCP and tetrahydro-S (TH-S) using 1.5% hydroxypropyl methylcellulose vehicle and beta-CD from Takeda Chemical Industries, Ltd., to simulate the procedure of Folkman and coworkers.(ABSTRACT TRUNCATED AT 250 WORDS)
Proia
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AD
Department of Pathology, Duke University Medical Center, Durham, NC 27710.
Hirakata
A
A
McInnes
J S
JS
Scroggs
M W
MW
Parikh
I
I
D019326:17-alpha-Hydroxyprogesterone; D000818:Animals; D003315:Cornea / Q000098:blood supply*; D003350:Cortodoxone / Q000031:analogs & derivatives / Q000627:therapeutic use; D003505:Cyclodextrins / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000627:therapeutic use; D006908:Hydroxyprogesterones / Q000627:therapeutic use; D008297:Male; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000517:prevention & control*; D009566:Nitrates; D017680:Potassium Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley; D012835:Silver Nitrate; D013256:Steroids / Q000627:therapeutic use*; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D006908:Hydroxyprogesterones; D009566:Nitrates; D017680:Potassium Compounds; D013256:Steroids; D047392:beta-Cyclodextrins; C039803:hydrocortisone sodium phosphate; C064089:beta-cyclodextrin tetradecasulfate; C009412:tetrahydro-11-deoxycortisol; D019326:17-alpha-Hydroxyprogesterone; D003907:Dexamethasone; D012835:Silver Nitrate; C023844:potassium nitrate; D003350:Cortodoxone; D006854:Hydrocortisone