Institute of Pharmaceutical Technology, Technische Universität Braunschweig, Mendelssohnstraße 1, 38106 Braunschweig, Germany.
J Control Release. 2014 Sep 10;189:54-64. doi: 10.1016/j.jconrel.2014.06.007. Epub 2014 Jun 14.
Lipid nanoemulsions and -suspensions are being intensively investigated as carriers for poorly water soluble drugs. The question on where model compounds or probes are localized within the dispersions has been the subject of several studies. However, only little data exists for pharmaceutically relevant molecules in dispersions composed of pharmaceutically relevant excipients. In this work, the localization of drugs and drug-like substances was studied in lipid nanoemulsions and -suspensions. Conclusions about the drug localization were drawn from the relations between lipid mass, specific particle surface area and drug load in the dispersions. Additionally, the achievable drug loads of the liquid and the solid lipid particles were compared. Nanoemulsions and -suspensions comprised trimyristin as lipid matrix and poloxamer 188 as emulsifier and were prepared with different well-defined particle sizes. These pre-formed dispersions were passively loaded with either amphotericin B, curcumin, dibucaine, fenofibrate, mefenamic acid, propofol, or a porphyrin derivative. The physico-chemical properties of the particles were characterized; drug load and lipid content were quantified by UV spectroscopy and high performance liquid chromatography, respectively. For all drugs the passive loading procedure was successful in both emulsions and suspensions. Solid particles accommodate drug molecules preferably at the particle surface. Liquid particles can accommodate drugs at the particle surface as well as in the core; the distribution between the two sites is drug specific. It is also drug specific whether solid or liquid particles yield higher drug loads. As a general rule, smaller particles led to higher drug loads than larger ones. Propofol and the porphyrin derivative displayed eutectic interaction with the lipid and crystal growth after loading, respectively.
脂质纳米乳液和混悬剂作为难溶性药物的载体受到了广泛的研究。模型化合物或探针在分散体中的定位问题已经成为了几个研究的主题。然而，对于由药用辅料组成的分散体中的药用相关分子，只有很少的数据存在。在这项工作中，研究了药物和类药物质在脂质纳米乳液和混悬剂中的定位。通过分散体中脂质质量、特定颗粒表面积和药物载药量之间的关系得出了关于药物定位的结论。此外，还比较了液体和固体脂质颗粒的可载药量。纳米乳液和混悬剂由三肉豆蔻酸甘油酯作为脂质基质和泊洛沙姆 188 作为乳化剂组成，并采用不同的明确定义的粒径制备。这些预形成的分散体通过被动载药法分别载有两性霉素 B、姜黄素、丁卡因、非诺贝特、甲芬那酸、丙泊酚或卟啉衍生物。对颗粒的物理化学性质进行了表征；通过紫外分光光度法和高效液相色谱法分别定量了药物载药量和脂质含量。对于所有药物，被动载药程序在乳液和混悬剂中均成功进行。固体颗粒优先在颗粒表面容纳药物分子。液体颗粒可以在颗粒表面以及核心内容纳药物；两种位置之间的分布是药物特异性的。固体颗粒还是液体颗粒产生更高的载药量也是药物特异性的。一般来说，较小的颗粒比较大的颗粒载药量更高。丙泊酚和卟啉衍生物分别与脂质发生共晶相互作用和载药后结晶生长。
