Effect of cyclodextrins on the structure and functions of blood components in vitro

Abstract

Cyclodextrins have been extensively used in various biomedical and pharmaceutical applications. In these applications, cyclodextrins administered in vivo would inevitably enter blood stream. However, there is not enough information on the hemocompatibility of cyclodextrins until now. In this study, we investigated the influences of cyclodextrins (α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin) on human blood components and functions in vitro, that is, morphology and lysis of red blood cells, structure and conformation of fibrinogen, complement activation, and blood coagulation. It was found that 10 mg/mL of α- or β-cyclodextrins caused abnormal red blood cell morphology and serious hemolysis, while γ-cyclodextrin at 10 mg/mL did not impair red blood cell membrane morphology and integrity. The three cyclodextrins at up to 10 mg/mL affected the local microstructure but did not change the conformation of fibrinogen. The three cyclodextrins from 0.01 to 1 mg/mL all significantly activated the complement system in a concentration-dependent way. The three cyclodextrins at up to 5 mg/mL in blood plasma did not cause significantly different coagulation times compared with the negative control. In addition, the three cyclodextrins at up to 5 mg/mL in whole blood did not cause abnormal coagulation parameters. These results provide significant information on blood safety of the three cyclodextrins for their biomedical and pharmaceutical applications.