Mohorcic M, Torkar A, Friedrich J, Kristl J, Murdan S
Laboratory of Biotechnology, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana, Slovenia.
Int J Pharm. 2007 Mar 6;332(1-2):196-201. doi: 10.1016/j.ijpharm.2006.09.042. Epub 2006 Sep 29.
The topical therapy of nail diseases is limited by the low permeability of drugs through the nail plate. To increase drug penetration, the integrity of the nail plate must be compromised to a certain extent. We hypothesised that keratinolytic enzymes might decrease the barrier properties of the nail plate by hydrolysing the nail keratins, and thereby enhance ungual drug permeation. To determine enzyme action on nail plates, nail clippings were incubated at 35 degrees C, in the presence of keratinase at optimal pH for 48h, after which the nail plates were examined using scanning electron microscopy. It was found that the enzyme acted on the intercellular matrix which holds nail cells together, such that corneocytes on the dorsal surface separated from one another and 'lifted off' the nail plate. In addition, the surface of the corneocytes was corroded. Permeation studies using modified Franz diffusion cells and bovine hoof membranes as a model for the nail plate showed that the enzyme enhanced drug permeation through the hoof membrane. The permeability and partition coefficients, and the drug flux were found to be significantly increased in the presence of the enzyme. We can conclude that the enzyme, via its hydrolytic action on nail plate proteins, could increase ungual drug delivery.
指甲疾病的局部治疗受到药物透过甲板渗透率低的限制。为了提高药物渗透，必须在一定程度上破坏甲板的完整性。我们推测，角质溶解酶可能通过水解指甲角蛋白来降低甲板的屏障特性，从而增强指甲药物渗透。为了确定酶对甲板的作用，将指甲剪屑在35摄氏度下，于最佳pH值的角蛋白酶存在下孵育48小时，之后使用扫描电子显微镜检查甲板。发现该酶作用于将指甲细胞固定在一起的细胞间基质，使得背表面的角质形成细胞彼此分离并“脱离”甲板。此外，角质形成细胞的表面被腐蚀。使用改良的Franz扩散池并以牛蹄膜作为甲板模型进行的渗透研究表明，该酶增强了药物透过蹄膜的渗透。发现在酶存在下渗透率和分配系数以及药物通量显著增加。我们可以得出结论，该酶通过其对甲板蛋白的水解作用，可以增加指甲药物递送。
