INCORPORATION OF VITAMIN-D-3 DERIVATIVES IN LIPOSOMES OF DIFFERENT LIPID TYPES
INCORPORATION OF VITAMIN-D-3 DERIVATIVES IN LIPOSOMES OF DIFFERENT LIPID TYPES
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DOI：
10.3109/10611869408996817
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发表时间：
1994-01-01
影响因子：
4.5
通讯作者：
STERNBERG, B
中科院分区：
文献类型：
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作者：
MERZ, K;STERNBERG, B
已知维生素D-3衍生物在表皮细胞的分化和增殖中是有效的。然而，在某些情况下，它们也可能表现出高钙活性，这可能是它们用于皮肤病学应用的严重限制。为了减少维生素D-3衍生物的副作用，提高药物在皮肤中的浓度，我们研究了维生素D-3衍生物在脂质体中的掺入，以优化其在银屑病治疗中的应用。发现超过80%的所提供药物的掺入率与A环、开放或闭合B环中的羟基数目以及类固醇分子侧链中的一些修饰相关的显著变化。一般而言，卵-PC脂质体中的掺入率比DMPC脂质体高约3%至10%。通过DSC和冷冻断裂电子显微镜获得的结果显示，已经在10摩尔%的浓度下通过掺入维生素D-3抑制DMPC双层的相变。这些结果支持了维生素D-3及其类似物被掺入脂双层中从而改变脂-脂相互作用的观点。
Vitamin D-3-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 D-3-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 D-3-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 D-3 already at a concentration of 10 mol%. These results support the idea that vitamin D-3 and its analoga investigated are incorporated into the lipid bilayer modifying there the lipid-lipid interactions.