Polymer-coated liposomes: Improved liposome stability and release of cytosine arabinoside (Ara-C)

Abstract

Liposomes of dimyristoylphosphatidylcholine (DMPC) or dipalmitoyl-phosphatidylcholine (DPPC), cholesterol (CHOL) and dicetylphosphate (DCP) containing Ara-C were prepared at pH4.5 and subsequently coated with a derivatized polysaccharide, O-palmitoylpullulan (OPP). Encapsulation efficiencies (EEF) of DMPC:CHOL: DCP (3:l:2mol ratio) and DPPC: CHOL: DCP (3:1:0.5 mol ratio) liposomes were respectively 28 and 40% before and 15 and 27% after coating with polymer. Stabilities of liposomes in sodium cholate (SC) concentrations up to 16mM at pH 5.6 or in SC solutions at pH7.4 were increased by coating with OPP. At pH 2.0 and 37°C, Ara-C was released at a slow rate, k^u_o (uncoated) or k^u_o (coated), for 24 h after an initial rapid release phase that lasted for about 6 h and the ratio k^u_o/k^c_o, was 1.9 and 5.7 for the DMPC:CHOL:DCP and the DPPC:CHOL:DCP compositions respectively. At pH7.4 and 37°C in the presence of l0 mM SC, the ratio k^u_o/k^c_o was 5.1 and 1.4 respectively. It is concluded that coating liposomes with OPP increases the potential of using liposomes as a drug delivery system in harsh environments such as encountered after oral administration, although the magnitude of the effect is dependent on the liposome composition.

Key Words:

• Liposome
• polymer-coated
• cytosine arabinoside
• stability