MODIFIED CYCLODEXTRIN SULFATES (MCDS11) HAVE POTENT INHIBITORY ACTIVITY AGAINST HIV AND HIGH ORAL BIOAVAILABILITY

Modified cyclodextrin sulphate (mCDS) in which lipophilic groups were introduced to cyclodextrin sulphate (CDS) was synthesized and proved more inhibitory to the replication of HIV-1 and HIV-2 than CDS or dextran sulphate (DS). The anti-coagulant activity of mCDS was lower than that of DS. Cyclodextrin phosphate (CDP) showed anti-HIV activity similar to that of CDS, and its anti-coagulant activity was even lower than that of mCDS. Flow cytometric analysis suggested that the mechanism of the anti-HIV-1 action of CDS, mCDS, and CDP is based on inhibition of HIV-1 binding to the cells. The peak blood concentration after oral administration of mCDS11(potassium tris[6-benzylthio-6-deoxy]-beta-cyclodextrin hexadecasulphate) to rabbits was about 1000 times higher than the concentration showing anti-HIV activity. The retention time in the blood was also long (blood half-life: 4 h). These results point to the potential usefulness of oral mCDS administration in the prophylaxis and/or therapy of HIV infections.