Drastic Improvements in Trapping Efficiency and Dispersibility for Phosphatidylcholine Liposomes in the Presence of Divalent Metal Ions

Abstract

The effects of divalent metal ions (Ca2+, Mg2+) on the physicochemical properties and dispersibility of phosphatidylcholine (PC) liposomes were examined by using an optical microscopy, and the measurements of trapping efficiency, lamellarity, zeta potential. The trapping efficiency of PC liposomes was markedly improved (ca. 8 times) in the presence of an equimolar amount of a divalent metal ion, and that bearing Ca2+ ions was then higher than that of liposomes bearing Mg2+ ions. Optical microscopy on PC liposomes showed that the formation of liposomes is markedly promoted by the addition of divalent metal ions. The lamellarity measurements revealed that liposome bearing divalent metal ions is a unilamellar structure; this gives a higher trapping efficiency of liposomes compared with a control. The lamellarity of liposomes bearing Ca2+ ions was then lower than that of those bearing Mg2+ ions. Liposomal solutions containing equimolar amount of divalent metal ions remained well dispersed for more than 1 month, whereas that without divalent metal ions exhibited a significant phase separation. The liposomes bearing Ca2+ ions then exhibited a better dispersibility than that of those bearing Mg2+ ions, because of their higher zeta potential. Finally, we concluded that the unilamellar liposomes formation with a high dispersibility is promoted by not only electrostatic repulsion between bilayers but also the spontaneous curvature of liposomal bilayers induced by bearing of divalent metal ions.