Institut für Pharmazie, Freie Universität Berlin, Berlin, Germany.
Int J Pharm. 2010 May 10;390(2):225-33. doi: 10.1016/j.ijpharm.2010.02.004. Epub 2010 Feb 11.
The modes of drug-particle interactions considerably influence drug delivery by nanoparticulate carrier systems and drug penetration into the skin. The exact mechanism of the drug loading and its release are still ambiguous. Therefore, the loading process, the interaction of the agent and the lipid matrix of solid lipid nanoparticles (SLNs) as well as the uptake of the loaded agent by skin lipids were analysed by electron spin resonance (ESR) and parelectric spectroscopy (PS) using spin probes (TEMPO, TEMPOL, and CAT-1) as model drugs differing in their lipophilicity. The spin probes were closely attached to the particles lipid surface (TEMPO) or located in the layers of the surfactant (CAT-1), respectively. Furthermore, two distinct sub-compartments on the SLN were found. To simulate the processes at the phase boundary SLN dispersion/skin, skin lipid mixtures were prepared and the transfer process of the spin labels was followed by ESR tomography. Transfer rates were related to the lipophilicity of the spin probe, the lipid mixture and the applied pharmaceutical formulation, SLN dispersion and aqueous solution, respectively. In particular, SLN accelerated in particular the distribution of the lipophilic agents.
药物-颗粒相互作用的模式极大地影响了纳米载体系统的药物传递和药物渗透进入皮肤。药物的加载和释放的确切机制仍不清楚。因此，通过电子自旋共振（ESR）和介电谱（PS）使用自旋探针（TEMPO、TEMPOL 和 CAT-1）分析了载药过程、药物与固体脂质纳米粒（SLN）的脂质基质的相互作用以及被皮肤脂质吸收的负载药物，这些自旋探针在亲脂性方面存在差异。自旋探针分别紧密附着在颗粒的脂质表面（TEMPO）或位于表面活性剂的层中（CAT-1）。此外，在 SLN 上还发现了两个明显不同的亚区室。为了模拟在相边界 SLN 分散体/皮肤处的过程，制备了皮肤脂质混合物，并通过 ESR 断层摄影术跟踪自旋标记物的转移过程。转移速率与自旋探针的亲脂性、脂质混合物和所应用的药物制剂、SLN 分散体和水溶液有关。特别是，SLN 特别加速了亲脂性药物的分布。
