Osanai S, Nakamura K
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Biomaterials. 2000 May;21(9):867-76. doi: 10.1016/s0142-9612(99)00210-0.
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.
为了提高脂质体包裹化学物质的释放效率，对新型pH敏感脂质体的设计与开发进行了研究。制备并表征了由L-α-二棕榈酰磷脂酰胆碱（DPPC）和聚羧酸组成的稳定脂质体。选择聚苹果酸（PMLA）作为融合剂，因为它在生理区域具有优异的生物降解性。引入聚苹果酸中的辛基在脂质体表面起锚定作用，对络合有显著贡献。从脂质体大小的变化方面研究了脂质体与聚酸之间的相互作用。讨论了聚合物分子量和用量对其特性，特别是融合的影响。通过脂质体的粒径、溶液的比浊法和共振能量转移测定法，评估了pH变化对脂质体聚集和融合等缔合行为的影响。从这些研究结果可以看出，随着溶液酸度的增加，络合更紧密的脂质体聚集和融合更积极。包裹在脂质体内水相中的钙黄绿素的泄漏随着pH值的降低而增加。pH对溶液中脂质体聚集的影响在定性上与泄漏行为相似。
