Effects of complexation between liposome and poly(malic acid) on aggregation and leakage behaviour.

ABSTRACT

The design and development of novel pH-sensitive liposomes were investigated to improve the release of liposome-encapsulated chemicals. Stable liposomes comprising of L-alpha-dipalmitoylphosphatidylcholine (DPPC) and poly(carboxylic acid) were prepared and characterized. Poly(malic acid) (PMLA) was chosen as a fusogen, because of its excellent biodegradability in physiological regions. Octyl groups introduced in the poly(malic acid) worked as anchors at the surface of the liposomes and made a remarkable contribution to complexing. The interaction between the liposomes and the polyacids was studied in terms of the change in size of the liposomes. The influences of molecular weight and amounts of polymer upon their characteristics, especially fusion, were discussed. The influences of pH change with respect to the association behavior of the liposomes such as aggregation and fusion were estimated by the particle size of the liposomes, turbidimetry of the solution and resonance energy transfer assay. From the results of these studies, it was shown that more tightly complexed liposomes aggregated and fused more positively with increasing acidity of the solution. The leakage of calcein entrapped in the inner aqueous phase of the liposomes increased with decreasing pH. The effect of pH on the liposome aggregation in a solution qualitatively paralleled that found in the leakage behavior.