Shape changes in the erythrocyte membrane induced by the absorption enhancer didecanoylphosphatidylcholine

The phospholipid didecanoylphosphatidylcholine (DDPC) has been shown to promote the nasal absorption of peptide drugs in rabbits. The absorption enhancing effect has been related to the cytotoxicity of DDPC; however, the mechanism of action is not completely elucidated. Thus, the aim of this study was to further understand the absorption promoting effect of DDPC by elucidation of the interaction of DDPC with plasma membranes (i.e. erythrocyte membranes). Incorporation of DDPC (0.01-0.27 mg/ml) into erythrocyte membranes was estimated and correlated with DDPC-induced shape changes of the cells as well as with DDPC-induced hemolysis. Incubation of erythrocytes for 30 min with DDPC resulted in discocyte-to-spherocyte shape changes with loss of concavity, as well as formation of a small number of echinocytes. Echinocyte formation might suggest that DDPC was incorporated into the outer leaflet of the erythrocyte membrane resulting in a crenated form. Spherocyte formation might result from incorporation of larger amounts of DDPC. The highest DDPC concentration induced cell aggregation. At this concentration, the amount of phospholipids in the erythrocyte membrane was increased by 5.3 mol% and the concentration-dependent hemolysis was almost complete. In contrast to the effect induced by DDPC, no shape changes of the erythrocyte were observed when incubated with long chain phosphatidylcholine (PC) from egg (0.05 mg/ml, 0.50 mg/ml). In this case only slight hemolysis was observed. Thus, these results supported previous assumptions that incorporation of medium chain phospholipids into cellular membranes happens very quickly, resulting in membrane disorders that might, in part, be responsible for the absorption enhancing effect and the cytotoxicity of the enhancer. (C) 1998 Elsevier Science B.V. All rights reserved.