Department of Pharmaceutical Technology, Institute of Pharmacy, Friedrich-Schiller-Universitat Jena, Jena, Germany.
Mol Pharm. 2010 Apr 5;7(2):350-63. doi: 10.1021/mp900130s.
Lipid nanoparticles and liposomal carrier systems are of growing interest for intravenous drug delivery due to their biocompatibility and targetability. It is, however, difficult to investigate their release behavior for lipophilic drugs under physiological conditions. This study describes a novel flow cytometric method studying drug transfer from such carrier systems to particles simulating physiological receptor sites. For this purpose, liquid and solid trimyristin nanoparticles or soybean phospholipid liposomes were loaded with the lipophilic fluorescent substances Nile red, temoporfin, and DiI. The transfer of these model drugs to large emulsion droplets was examined by flow cytometry. Transfer of DiI to differently sized acceptor emulsions was also monitored by separating donor and acceptor particles using ultracentrifugation. Flow cytometry revealed a completion of transfer within a few minutes for Nile red and temoporfin at considerable amounts of transferred dye. In contrast, the highly lipophilic DiI transferred over a period of weeks only for a small percentage of the dye. Ultracentrifugation results confirmed this for DiI and indicated a dependence of transfer characteristics on the acceptor surface area. Nile red transfer into a bulk oil phase as alternative acceptor system was also very slow. Flow cytometry seems to be well suited to study the intrinsic transfer of fluorescent lipophilic substances, as no kinetic hindrances like dialysis bags nor separation steps are required. Additional detailed experiments will, however, be necessary to elucidate the prevalent transfer mechanisms completely.
脂质纳米颗粒和脂质体载体系统由于其生物相容性和靶向性，对于静脉内药物递送越来越受到关注。然而，在生理条件下研究亲脂性药物从这些载体系统中的释放行为具有一定难度。本研究描述了一种新颖的流动细胞术方法，用于研究此类载体系统向模拟生理受体部位的颗粒中药物的传递。为此，将亲脂性荧光物质尼罗红、替莫泊芬和 DiI 装载于液体和固体三硬脂酰基磷脂酰甘油纳米颗粒或大豆磷脂脂质体中。通过流式细胞术检查这些模型药物向大乳液液滴的传递。还通过使用超速离心分离供体和受体颗粒来监测 DiI 向不同大小的接受乳液的传递。流式细胞术显示，尼罗红和替莫泊芬在相当大量转移染料的情况下，在几分钟内完成了转移。相比之下，高度亲脂性的 DiI 仅在一小部分染料转移，需要数周时间。超速离心结果证实了 DiI 的情况，并表明转移特性取决于接受体表面积。将 DiI 转移到替代的 bulk oil 相作为接受体系统也非常缓慢。流式细胞术似乎非常适合研究荧光亲脂性物质的内在转移，因为不需要像透析袋那样的动力学障碍或分离步骤。然而，需要进行更多详细的实验来完全阐明普遍的转移机制。
