Abstract
Liposomes of dimyristoylphosphatidylcholine (DMPC) or dipalmitoylphosphatidylcholine (DPPC), cholesterol (CHOL) and dicetylphosphate (DCP) containing Ara-C were prepared at pH 4.5 and subsequently coated with a derivatized polysaccharide, O-palmitoylpullulan (OPP). Encapsulation efficiencies (EEF) of DMPC:CHOL:DCP (3:1:2 mol 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 16 mM at pH 5.6 or in SC solutions at pH 7.4 were increased by coating with OPP. At pH 2.0 and 37 degrees C, Ara-C was released at a slow rate, kuo (uncoated) or kco (coated), for 24 h after an initial rapid release phase that lasted for about 6 h and the ratio kuo/kco, was 1.9 and 5.7 for the DMPC:CHOL:DCP and the DPPC:CHOL:DCP compositions respectively. At pH 7.4 and 37 degrees C in the presence of 10 mM SC, the ratio kuo/kco 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.
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