The hemolytic properties of chemically modified cyclodextrins

The hemolytic properties of natural cyclodextrins, especially of the more common cyclomaltoheptaose entity, severely hamper their potential use as carriers in pharmaceutical applications where parenteral administration is concerned. A systematic investigation on the role of chemical modifications with regard to the hemolytic character was carried out involving C-6 branched neutral, anionic, cationic and amphoteric derivatives. From these data, conclusions have been drawn about the charge and the geometry of the modification: (i) Substitution at primary hydroxyl groups usually decreases the hemolytic character and the geometry of the substituent affects the hemolytic property; (ii) introduction of an amino group, resulting in a positive charge at physiological pH, decreases the hemolytic character; (iii) negative charges are comparatively less effective in reducing the hemolytic character; (iv) zwitterionic groups seem to enhance the hemolytic character of the cyclodextrin molecule.