The Hemolytic Properties of Chemically Modified Cyclodextrins

The hemolytic properties of naturalcyclodextrins, especially of the more commoncyclomaltoheptaose entity, severely hamper theirpotential use as carriers in pharmaceuticalapplications where parenteral administration isconcerned. A systematic investigation on the role ofchemical modifications with regard to the hemolyticcharacter was carried out involving C-6 branchedneutral, anionic, cationic and amphoteric derivatives.From these data, conclusions have been drawnabout the charge and the geometry of the modification: (i)Substitution at primary hydroxyl groups usuallydecreases the hemolytic character and the geometry ofthe substituent affects the hemolytic property; (ii)introduction of an amino group, resulting in apositive charge at physiological pH, decreases thehemolytic character; (iii) negative charges arecomparatively less effective in reducing the hemolyticcharacter; (iv) zwitterionic groups seem to enhancethe hemolytic character of the cyclodextrin molecule.