Chemical Modifications of Heparin. II. Hydrophobization of Partially N-Desulfated Heparin

Abstract

In order to hydrophobize heparin, dodecanal, cholic acid and stearic acid were conjugated, respectively, to partially N-desulfated heparin with the formation of imine bonds in the case of dodecanal and amide bonds in the case of the two latter compounds. It was found that the three conjugates were aggregated in aqueous solution with the formation of-300 nm aggregates. The conjugates retained the anticoagulant activity of the parent heparin according to in vitro tests. In vivo, slightly prolonged activity was observed after s.c. injection. The activity lasted for at least 2 hours after i.v. injection suggesting that aggregates of hydrophobized heparin were not captured by the reticuloendothelial system. These new water dispersed aggregates are of potential interest for the transport and slow release of hydrophobic drugs in blood either as macromolecular prodrugs or after molecular microencapsulation, and for oral administration.