Tetrahydro-derivatives of cortisone promote granulomatous tissue angiogenesis in vivo on topical application in hyaluronan.

Hyaluronan is an essential component of the extracellular matrix and alters the quality of wound healing as well as modulating angiogenesis. It is also used as a topical and i.v. drug delivery system. We have previously reported that cortisone in hyaluronan gel inhibits granulomatous tissue angiogenesis, as does tetrahydrocortisol (THF) administered s.c. We have investigated the effects of tetrahydrocortisone (THE) and THF administered s.c. on granulomatous tissue angiogenesis, and compared this with their topical administration in hyaluronan. Carmine/gelatin vascular casts of murine chronic granulomatous air pouches were formed and the vascularity index calculated as μg carmine/mg granuloma dry mass. THF inhibited angiogenesis as previously reported; however, THE stimulated angiogenesis significantly. On topical application in 2.5% hyaluronan both steroids dramatically stimulated granulomatous tissue angiogenesis, THE by 100% and THF by 300% at 1mg/kg. Previous work has shown that topical hyaluronan alone has little effect on granulomatous tissue angiogenesis. Thus the topical application of the tetrahydro-steroid derivatives results in the stimulation of angiogenesis and converts the angiostatic properties of THF to an angiogenic profile. These formulations may therefore have potential as topical therapies, e.g. for the acceleration of wound healing.