Merz K, Sternberg B
Institute of Organic and Macromolecular Chemistry, Friedrich-Schiller-University Jena, Germany.
J Drug Target. 1994;2(5):411-7. doi: 10.3109/10611869408996817.
Vitamin D3-derivatives are known to be effective in differentiation and proliferation of epidermal cells. However, under certain circumstances, they also may show a hypercalcamic activity which can be a serious limitation in their use for dermatological application. For keeping small the negative side effects of vitamin D3-derivatives and for increasing the drug concentration in the skin we investigated their incorporation in liposomes to optimize their use for psoriasis treatment. The incorporation of vitamin D3-derivatives in liposomes of different lipid composition was studied by HPLC, DSC and freeze-fracture electron microscopy. Incorporation rates of more than 80% of the offered drug were found with significant variations related to the number of hydroxyl-groups in the A-ring, opened or closed B-ring, and some modifications in the side chain of the steroid-molecules. In general, the incorporation rates in egg-PC liposomes have been of about 3% up to 10% higher than in DMPC liposomes. Results, obtained by DSC and freeze-fracture electron microscopy, show a depression of the phase transition of DMPC bilayers by incorporation of vitamin D3 already at a concentration of 10 mol%. These results support the idea that vitamin D3 and its analoga investigated are incorporated into the lipid bilayer modifying there the lipid-lipid interactions.
已知维生素D3衍生物对表皮细胞的分化和增殖有效。然而，在某些情况下，它们也可能表现出高钙活性，这在其用于皮肤病学应用时可能是一个严重的限制。为了尽量减少维生素D3衍生物的副作用并提高其在皮肤中的药物浓度，我们研究了将它们包封于脂质体中以优化其用于银屑病治疗的效果。通过高效液相色谱法（HPLC）、差示扫描量热法（DSC）和冷冻断裂电子显微镜对维生素D3衍生物在不同脂质组成的脂质体中的包封情况进行了研究。发现所提供药物的包封率超过80%，且与A环中羟基的数量、B环的开环或闭环以及甾体分子侧链的一些修饰存在显著差异。一般来说，维生素D3衍生物在蛋黄卵磷脂（egg-PC）脂质体中的包封率比在二肉豆蔻酰磷脂酰胆碱（DMPC）脂质体中的高约3%至10%。通过DSC和冷冻断裂电子显微镜获得的结果表明，在维生素D3浓度为10 mol%时，其包封就会使DMPC双层膜的相变温度降低。这些结果支持了以下观点：所研究的维生素D3及其类似物被包封于脂质双层中，从而改变了脂质-脂质相互作用。
