Hossin B, Rizi K, Murdan S
Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
Eur J Pharm Biopharm. 2016 May;102:32-40. doi: 10.1016/j.ejpb.2016.02.009. Epub 2016 Feb 23.
We hypothesised that Hansen Solubility Parameters (HSPs) can be used to predict drug-nail affinities. Our aims were to: (i) determine the HSPs (δD, δP, δH) of the nail plate, the hoof membrane (a model for the nail plate), and of the drugs terbinafine HCl, amorolfine HCl, ciclopirox olamine and efinaconazole, by measuring their swelling/solubility in organic liquids, (ii) predict nail-drug interactions by comparing drug and nail HSPs, and (iii) evaluate the accuracy of these predictions using literature reports of experimentally-determined affinities of these drugs for keratin, the main constituent of the nail plate and hoof. Many solvents caused no change in the mass of nail plates, a few solvents deswelled the nail, while others swelled the nail to varying extents. Fingernail and toenail HSPs were almost the same, while hoof HSPs were similar, except for a slightly lower δP. High nail-terbinafine HCl, nail-amorolfine HCl and nail-ciclopirox olamine affinities, and low nail-efinaconazole affinities were then predicted, and found to accurately match experimental reports of these drugs' affinities to keratin. We therefore propose that drug and nail Hansen Solubility Parameters may be used to predict drug-nail interactions, and that these results can assist in the design of drugs for the treatment of nail diseases, such as onychomycosis and psoriasis. To our knowledge, this is the first report of the application of HSPs in ungual research.
我们假设汉森溶解度参数（HSPs）可用于预测药物与指甲的亲和力。我们的目标是：（i）通过测量药物盐酸特比萘芬、盐酸阿莫罗芬、环吡酮胺和艾氟康唑在有机液体中的溶胀/溶解度，确定指甲板、蹄膜（指甲板的模型）以及这些药物的汉森溶解度参数（δD、δP、δH）；（ii）通过比较药物和指甲的汉森溶解度参数来预测指甲与药物的相互作用；（iii）利用这些药物对指甲板和蹄的主要成分角蛋白的实验测定亲和力的文献报道，评估这些预测的准确性。许多溶剂对指甲板的质量没有影响，少数溶剂使指甲收缩，而其他溶剂则使指甲有不同程度的膨胀。手指甲和脚趾甲的汉森溶解度参数几乎相同，而蹄的汉森溶解度参数相似，只是δP略低。据此预测出指甲与盐酸特比萘芬、指甲与盐酸阿莫罗芬以及指甲与环吡酮胺的亲和力较高，而指甲与艾氟康唑的亲和力较低，并且发现这些预测与这些药物对角蛋白亲和力的实验报告准确匹配。因此，我们建议药物和指甲的汉森溶解度参数可用于预测药物与指甲的相互作用，并且这些结果有助于设计治疗指甲疾病（如甲癣和银屑病）的药物。据我们所知，这是汉森溶解度参数在指甲研究中的首次应用报告。
