Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854, USA.
Langmuir. 2011 Aug 2;27(15):9131-8. doi: 10.1021/la200038a. Epub 2011 Jul 6.
Surfactant amphiphilic macromolecules (AMs) were complexed with a 1:1 ratio of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), either by a coevaporation (CE) or postaddition (PA) method, to form AM-lipid complexes with enhanced drug delivery applications. By characterizing the surfactant-lipid interactions, these heterogeneous drug delivery systems can be better controlled and engineered for optimal therapeutic outcomes. In this study, the physical interactions between DOPE:DOTAP liposomes and AM surfactants were investigated. Langmuir film balance and isothermal calorimetry studies showed cooperative intermolecular interactions between pure lipids and AM in monolayers and high thermostability of structure formed by the addition of AM micelles to DOTAP:DOPE vesicles in buffer solution respectively. Increasing the AM weight ratio in the complexes via the CE method led to complete vesicle solubilization--from lamellar aggregates, to a mixture of coexisting vesicles and micelles, to mixed micelles. Isothermal calorimetry evaluation of AM-lipid complexes shows that, at higher AM weight ratios, PA-produced complexes exhibit greater stability than complexes at lower AM weight ratios. Similar studies show that AM-lipid complexes produced by the CE methods display stronger interactions between AM-lipid components than complexes produced by the PA method. The results suggest that the PA method produces vesicles with AM molecules associated with its outer leaflet only (i.e., an AM-coated vesicle), while the CE method produces complexes ranging from mixed vesicles to mixed micelle in which the AM-lipid components are more intimately associated. These results will be helpful in the design of AM-lipid complexes as structurally defined, stable, and effective drug delivery systems.
两亲性大分子（AMs）与 1,2-二油酰基-3-三甲铵丙烷（DOTAP）和 1,2-二油酰基-sn-甘油-3-磷酸乙醇胺（DOPE）以 1:1 的摩尔比通过共蒸发（CE）或后添加（PA）方法复合，形成具有增强药物递送应用的 AM-脂质复合物。通过表征表面活性剂-脂质相互作用，可以更好地控制和设计这些异质药物递送系统，以获得最佳的治疗效果。在这项研究中，研究了 DOPE:DOTAP 脂质体和 AM 表面活性剂之间的物理相互作用。Langmuir 膜天平法和等温量热法研究表明，在单层中纯脂质和 AM 之间存在协同的分子间相互作用，并且在缓冲溶液中通过添加 AM 胶束到 DOTAP:DOPE 囊泡中形成的结构具有高的热稳定性。通过 CE 方法增加复合物中 AM 的重量比会导致囊泡完全溶解——从层状聚集体到共存的囊泡和胶束混合物，再到混合胶束。等温量热法评估 AM-脂质复合物表明，在较高的 AM 重量比下，PA 产生的复合物比在较低 AM 重量比下产生的复合物具有更大的稳定性。类似的研究表明，CE 方法制备的 AM-脂质复合物中 AM-脂质成分之间的相互作用强于 PA 方法制备的复合物。结果表明，PA 方法产生的囊泡中只有 AM 分子与外层结合（即，AM 涂层囊泡），而 CE 方法产生的复合物范围从混合囊泡到混合胶束，其中 AM-脂质成分更紧密地结合在一起。这些结果将有助于设计作为结构明确、稳定和有效的药物递送系统的 AM-脂质复合物。
