Heparin penetration into and permeation through human skin from aqueous and liposomal formulations in vitro
Heparin penetration into and permeation through human skin from aqueous and liposomal formulations in vitro
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DOI：
10.1016/s0378-5173(01)00832-8
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发表时间：
2001-10-09
影响因子：
5.8
通讯作者：
Imanidis, G
中科院分区：
文献类型：
--
作者：
Betz, G;Nowbakht, P;Imanidis, G
采用热分离表皮膜法和真皮层法研究了未分离肝素（UH）和低分子量肝素（LMWH）在体外人体皮肤中的转运，评价了含磷脂(R) 80 （PL80）和鞘磷脂（SM）的脂质体制剂对肝素在皮肤组织中的分布的影响。用生物法测定肝素浓度。通过测定经皮失水来表征皮肤的屏障特性。肝素未在表皮膜上均匀渗透。低分子肝素对表皮膜的渗透明显大于UH， UH的积累主要局限于角质层的最外层，而低分子肝素则渗透到更深的表皮层。仅在PL80脂质体制剂中检测到UH对表皮的渗透。低分子肝素的渗透程度与配方无关，但与含水配方相比，低分子肝素有在PL80表皮深层积聚的趋势。因此，分子量和脂质体配方影响肝素在表皮中的渗透模式。目前还不能确定在毛细血管处达到的低分子肝素浓度是否足以发挥药理作用。在SM脂质体的存在下，UH在真皮层的蓄积显著增强，渗透滞后时间延长。(C) 2001 Elsevier Science B.V.版权所有
The transport of unfractionated (UH) and low molecular weight Heparin (LMWH) in human skin was investigated in vitro using heat separated epidermal membrane and dermis and the effect of liposomal formulations with Phospholipon(R) 80 (PL80) and Sphingomyelin (SM) was assessed, The distribution or Heparin within skin tissue was studied by the tape stripping method. Heparin concentrations were measured with a biological assay. Transepidermal water loss was determined to characterize barrier properties of skin. No consistent permeation of Heparin through epidermal membrane was detected. Penetration into the epidermal membrane was for LMWH significantly greater than for UH, Accumulation of UH was largely restricted to the outermost layers of the stratum corneum while LMWH penetrated into deeper epidermal layers. UH penetration into epidermis was detected for the PL80 liposomal formulation only. The extent of LMWH penetration was independent of the formulation, LMWH, however, showed a trend to accumulate in deeper epidermal layers for the PL80 compared to the aqueous formulation. Thus, molecular weight and liposomal formulations influenced the penetration pattern of Heparin in the epidermis. It can not be concluded whether the concentration of LMWH achieved at the blood capillaries is sufficient to exert a phamacological effect. UH permeated readily through dermis irrespectively of formulation and its accumulation in the dermis was significantly enhanced and its lag time of permeation increased in the presence of SM liposomes. (C) 2001 Elsevier Science B.V. All rights reserved.