Brown M B, Marriott C, Martin G P
Department of Pharmacy, King's College London, England.
Int J Tissue React. 1995;17(4):133-40.
Hyaluronan is a glycosaminoglycan and has a protective, shock-absorbing and structure-stabilizing role in connective tissue. Recently, it has been suggested that hyaluronan can be used as a controlled and localized delivery vehicle for diclofenac in the treatment of a variety of conditions including osteoarthritic pain, basal cell carcinoma and actinic keratosis. The aim of this study was to examine the effects of hyaluronan on the in-vitro diffusion and deposition of diclofenac within the skin. The studies involved full thickness, epidermal sheet and stratum corneum human skin sections in an in-vitro Franz cell model, in which the diffusion and deposition of 14C-labelled diclofenac and 3H-labelled hyaluronan was investigated. The results showed that the diffusion of 14C-labelled diclofenac was sustained and controlled by hyaluronan as compared to a buffer control, that a depot or reservoir of the drug was formed in the epidermis and that it was probably this layer that determined the rate of release of diclofenac within the skin. 3H-labelled hyaluronan was found to penetrate all layers of the skin, although the rate of diffusion was much slower than that of labelled diclofenac. Again, most of the activity was found to be retained within the epidermis, which supports the hypothesis of the importance of this layer in the mode of action. The presence within the epidermis of potential receptors for hyaluronan has recently been confirmed, and this may partially explain the findings of the present in-vitro studies.
透明质酸是一种糖胺聚糖，在结缔组织中具有保护、减震和稳定结构的作用。最近，有人提出透明质酸可作为双氯芬酸的控释和局部递送载体，用于治疗包括骨关节炎疼痛、基底细胞癌和光化性角化病在内的多种病症。本研究的目的是研究透明质酸对双氯芬酸在皮肤内的体外扩散和沉积的影响。这些研究在体外Franz细胞模型中使用了全层、表皮片和角质层人皮肤切片，研究了14C标记的双氯芬酸和3H标记的透明质酸的扩散和沉积情况。结果表明，与缓冲液对照相比，14C标记的双氯芬酸的扩散受到透明质酸的持续控制，药物在表皮中形成了储存库或贮库，可能正是这一层决定了双氯芬酸在皮肤内的释放速率。发现3H标记的透明质酸可穿透皮肤的所有层，尽管其扩散速率比标记的双氯芬酸慢得多。同样，大部分活性物质被发现保留在表皮内，这支持了该层在作用方式中重要性的假设。最近已证实表皮中存在透明质酸的潜在受体，这可能部分解释了本体外研究的结果。
