Effect of sulfated beta-cyclodextrin, a water soluble cycloamylose, on the promotion and/or inhibition of angiogenesis.

Abstract

Previous studies have reported that sulfated b b-cyclodextrin, a naturally occurring cycloamylose built up from six to eight glucopyranose units, when administered alone promotes angiogenesis, but administered with an angiostatic steroid inhibits angiogenesis in the cick embryo bioassay. In our experiments sulfated b b-cyclodextrin has been shown to possess many properties unrelated to its classical functions in the promotion and inhibition of angiogenesis that were not previously described. We studied the angiogenic and angiostatic properties of b b-cyclodextrin in a subcutaneous plastic sponge model in mice. We realized two set of experiments. In each set mice were randomized into five groups (n= 5 mice). The first group was treated with sulfated b b-cyclodextrin (200 ng), the second group was treated with sulfated b b-cyclodextrin (2000 ng), the third group received unsubstituted b b-cyclodextrin (2000 ng), the fourth group was treated with sulfated b b-cyclodextrin (20000 ng) and the last group was used as a control group. In all groups compounds were administered intraperitoneally 4 days after subcutaneous implantation of a sterile polyvinyl sponge on day 0, controls were not treated. Cyclodextrin administered alone at low drug concentration (200 ng) promoted angiogenesis and increased the development of venules in the sponge matrix. However, cyclodextrin administered at high drug concentration (2000 and 20 000 ng) reduced the vessel index in the sponge and areas of microhemorrhages were observed. From our results we propose that b b-cyclodextrin contains both a promoter and an inhibitor of angiogenesis and that the activation of both is drug concentration dependent.