Surface charge modulation of liposomes by enzymatic hydrolysis of macrocyclic 1,2-dotriacontanedioyl-sn-glycero-3-phosphocholine.

1,2-Dotriacontanedioyl-sn-glycero-3-phosphocholine (dTPC) was synthesized, and by a sonication method, dTPC was transformed into liposomes with physical features (charge, size, gel-to-liquid crystalline phase transition constants, etc.) similar to those of liposomes made of acyclic 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). Quantitative enzymatic assays using phospholipases A2 and C showed that dTPC was comparable with or better than DPPC as a substrate. Remarkably, the liposomes assembled from a mixture of dTPC and 1,2-distearyl-sn-glycero-3-phosphocholine were converted rapidly into anionic liposomes at pH 7 by the action of phospholipase A2, keeping their vesicular structure and exposing CO2H groups of the lysolipids of dTPC on the membrane surface. The use of dTPC is discussed in conjunction with the enzyme-catalyzed modification of the liposomes.