Béduneau Arnaud, Saulnier Patrick, Anton Nicolas, Hindré François, Passirani Catherine, Rajerison Holisoa, Noiret Nicolas, Benoit Jean-Pierre
Inserm U646, Université d'Angers, Angers F-49100, France.
Pharm Res. 2006 Sep;23(9):2190-9. doi: 10.1007/s11095-006-9061-y. Epub 2006 Aug 9.
To develop from an original process, a novel generation of stealth lipidic nanocapsules in order to improve the lipophilic drug delivery in accessible sites.
Nanocapsules covered by PEG1500 stearate were obtained by a low energy emulsification method. Conductivity measurements and ternary diagram were performed to describe the formulation mechanism. Hemolytic dosage CH50 and pharmacokinetic study in rats have been achieved in order to study the stealth properties of nanocapsules.
Transition from an O/W emulsion to a w/O/W emulsion was necessary to produce PEG1500 stearate nanocapsules. Interestingly nanocapsules with a size around 26 nm and a polydispersity index inferior to 0.1 were obtained. The CH50 test has revealed a very weak complement consumption in the presence of such nanocapsules. Moreover, after intravenous injection into rats, PEG1500 stearate nanocapsules exhibited long circulating properties. The experimental data support the concept of steric repulsion of the surface towards proteins, displayed by nanocapsules covered with PEG1500 stearate. These in vivo results were in agreement with the PEG1500 density calculated at the nanocarrier surface.
Injectable drug carriers have been developed. Their long-circulating properties could confer them a strong potential for lipophilic drug targeting.
从原始工艺开发新一代隐形脂质纳米胶囊，以改善亲脂性药物在可及部位的递送。
通过低能乳化法获得由硬脂酸聚乙二醇1500覆盖的纳米胶囊。进行电导率测量和三元相图以描述制剂形成机制。为研究纳米胶囊的隐形特性，已完成大鼠的溶血剂量CH50和药代动力学研究。
要制备硬脂酸聚乙二醇1500纳米胶囊，从水包油乳液转变为油包水包油乳液是必要的。有趣的是，获得了尺寸约为26 nm且多分散指数低于0.1的纳米胶囊。CH50测试表明，在此类纳米胶囊存在下补体消耗非常少。此外，硬脂酸聚乙二醇1500纳米胶囊经静脉注射到大鼠体内后表现出长循环特性。实验数据支持了由硬脂酸聚乙二醇1500覆盖的纳米胶囊所表现出的表面对蛋白质的空间排斥概念。这些体内结果与在纳米载体表面计算的聚乙二醇1500密度一致。
已开发出可注射的药物载体。它们的长循环特性可能使其在亲脂性药物靶向方面具有强大潜力。
