Prüfer K, Merz K, Barth A, Wollina U, Sternberg B
Dermatology Department, Friedrich-Schiller-University Jena, Germany.
J Drug Target. 1994;2(5):419-29. doi: 10.3109/10611869408996818.
The influence of different liposomal qualities, loaded with a variety of vitamin D3-analogues, on the proliferation and interleucine 1 alpha-release (IL-1 alpha) of human keratinocytes was examined by fluorimetric and colorimetric measurements to optimize their use for psoriasis treatment. In comparison, the effects of the free drugs, as 25-hydroxyvitamin D3, calcipotriol, and calcitriol, as well as of empty liposomes have been studied. At the interaction between empty liposomes (< 200 nm) and HaCaT-cells has been looked by electron microscopy. Empty liposomes, made of DMPC as well as of egg-PC, can be used as drug carrier without any inhibiting effect on the proliferation of human keratinocytes at lipid concentrations of < 10(-4) M. Under the influence of the free drugs investigated an inhibition of cell growth as well as of the IL 1 alpha-release was measured at drug concentrations of > or = 10(-8) M. In comparison the related liposomal drug formulations didn't show any diminishing in the proliferation effects caused by the free drugs. A significant improvement, however, was only found in the action of DMPC-incorporated 25-hydroxyvitamin D3 at drug concentration of 10(-7) M. These results suggest that there is no remarkable improvement in the action of liposomal incorporated vitamin D3-analogues neither related to their proliferation nor their IL1 alpha-releasing effects. The influence of liposomal incorporated vitamin D3-analogues in keeping small their negative side effects has to be investigated at a more relevant model.
通过荧光和比色测量法，研究了负载多种维生素D3类似物的不同脂质体性质对人角质形成细胞增殖和白细胞介素1α释放（IL-1α）的影响，以优化其在银屑病治疗中的应用。相比之下，还研究了游离药物（如25-羟基维生素D3、卡泊三醇和骨化三醇）以及空脂质体的作用。通过电子显微镜观察了空脂质体（<200 nm）与HaCaT细胞之间的相互作用。由二肉豆蔻酰磷脂酰胆碱（DMPC）以及蛋黄卵磷脂（egg-PC）制成的空脂质体，在脂质浓度<10^(-4) M时，可作为药物载体，对人角质形成细胞的增殖没有任何抑制作用。在所研究的游离药物的影响下，在药物浓度≥10^(-8) M时，可检测到细胞生长以及IL-1α释放受到抑制。相比之下，相关的脂质体药物制剂并未显示出游离药物引起的增殖效应有任何减弱。然而，仅在药物浓度为10^(-7) M时，发现掺入DMPC的25-羟基维生素D3的作用有显著改善。这些结果表明，脂质体掺入的维生素D3类似物在其增殖或IL-1α释放作用方面没有显著改善。必须在更相关的模型中研究脂质体掺入的维生素D3类似物在保持其负面副作用较小方面的影响。
