Florence Pilard

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.

A sensitive and specific enzyme immunoassay for cyclomaltoheptaose and some derivatives

Antibodies were raised against cyclomaltoheptaose (beta-cyclodextrin), providing a highly sensitive enzyme immunoassay for beta-cyclodextrin and some derivatives with a detection limit of 120 pg/mL. Investigations of cross-reactivities with a wide variety of linear and cyclic maltooligosaccharides demonstrate that the antibodies are highly specific for cyclomaltoheptaose and a number of derivatives. The epitope is probably located on the secondary hydroxyl groups of the rim side. This enzyme immunoassay is shown to be suitable to detect cyclomaltoheptaose in urine and in plasma.