Lehrstuhl für Pharmazeutische Technologie, Friedrich-Schiller-Universität Jena, Lessingstr. 8, D-07743 Jena, Germany.
Eur J Pharm Sci. 2009 Oct 8;38(3):238-48. doi: 10.1016/j.ejps.2009.07.012. Epub 2009 Aug 5.
Cholesteryl nonanoate (CN), myristate (CM), palmitate (CP) and oleate (CO) alone or in combination were evaluated as matrix lipids for the preparation of supercooled smectic nanoparticles with a high stability against recrystallization during storage. The phase behavior of the cholesterol esters in the bulk was studied by polarizing light microscopy, differential scanning calorimetry (DSC) and small angle X-ray scattering (SAXS). Colloidal dispersions with pure and mixed cholesterol ester matrices were prepared by high-pressure melt homogenization and characterized by photon correlation spectroscopy, laser diffraction combined with polarizing intensity differential scattering, DSC and SAXS. The morphology of selected formulations was studied by freeze-fracture electron microscopy. All smectic nanoparticles with a mixed cholesterol ester matrix were stable against recrystallization when stored at room temperature. Nanoparticles with a pure CN and mixed CM/CN matrix with a high fraction of CN (60% of the whole lipid matrix) could even be stored at 4 degrees C for at least 18 months without any recrystallization. As smectic nanoparticles are studied especially with regard to parenteral administration of lipophilic drugs, the cytotoxicity of selected formulations was compared with that of a clinically used colloidal fat emulsion (Lipofundin MCT) in the murine fibroblast cell line L929 using the sulforhodamine B assay. The supercooled smectic nanoparticle formulations display a good overall cell compatibility although in some cases their cytotoxicity was slightly higher than that of Lipofundin MCT.
胆固醇壬酸酯（CN）、肉豆蔻酸酯（CM）、棕榈酸酯（CP）和油酸酯（CO）单独或组合用作基质脂质，用于制备超冷层状纳米粒子，在储存过程中具有高稳定性，防止重结晶。通过偏光显微镜、差示扫描量热法（DSC）和小角 X 射线散射（SAXS）研究胆固醇酯在本体中的相行为。通过高压熔融匀化制备具有纯和混合胆固醇酯基质的胶体分散体，并通过光子相关光谱法、激光衍射与偏振强度差散射相结合、DSC 和 SAXS 进行表征。通过冷冻断裂电子显微镜研究了选定配方的形态。当在室温下储存时，具有混合胆固醇酯基质的所有层状纳米粒子都能稳定地防止重结晶。具有纯 CN 和混合 CM/CN 基质（CN 占整个脂质基质的 60%）的纳米粒子甚至可以在 4°C 下储存至少 18 个月而不会发生任何重结晶。由于层状纳米粒子尤其被研究用于亲脂性药物的肠胃外给药，因此使用 Sulforhodamine B 测定法在小鼠成纤维细胞系 L929 中比较了选定配方的细胞毒性与临床使用的胶体脂肪乳剂（Lipofundin MCT）的细胞毒性。尽管在某些情况下，超冷层状纳米粒子制剂的细胞毒性略高于 Lipofundin MCT，但它们具有良好的整体细胞相容性。
