Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
Department of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck, University of London, Malet Street, London WC1E 7HX, UK.
Int J Pharm. 2022 Feb 25;614:121437. doi: 10.1016/j.ijpharm.2021.121437. Epub 2021 Dec 29.
A nail patch is an attractive option for the topical treatment of onychomycosis, although no product is commercially available. We previously identified optimal nail patch formulations for two anti-onychomycotic drugs, based on their properties, as well as those of the other patch components. In this paper, our aim was to further investigate the potential of the patch formulations as topical nail medicines, in particular, whether the drug-in-adhesive patches release drug which then permeates into and through the nail plate and show anti-fungal efficacy, and whether and to what extent they remain adhered to the human nail plate in vivo when tested over 2 week durations. In addition, the influence of the drug (amorolfine HCl, ciclopirox olamine) and PSA (Duro-Tak 2852 or Duro-Tak 202A) on these parameters was determined. We found that both the nature of the drug and of the PSA influenced in vitro drug release. The nature of the drug, but not that of the PSA, influenced ungual drug permeation through human nail clippings, with considerably greater (almost double) permeation for ciclopirox olamine, the smaller and less lipophilic molecule. In vivo residence, tested with 3 out of the 4 patches, excluding the patch where ciclopirox olamine degraded with time, showed greater residence on toenails compared to fingernails reflecting their far lesser exposure to environmental stresses during daily activities. In vivo residence was enhanced when the patch was cut to the shape of the nail, was applied at bedtime, and when a clear colourless nail varnish was applied on top of the patch to 'seal' it into place on the nail. Comparison of the patches indicated greater residence of Duro-Tak 202A containing patches over those containing Duro-Tak 2852. Amorolfine HCl in Duro-Tak 202A based patch also showed antifungal efficacy in contrast to Duro-Tak 2852-based patch, and is particularly promising for further development as a potential toenail medicine, remaining almost fully adhered to toenails for at least two weeks.
指甲贴片是治疗甲真菌病的一种有吸引力的局部治疗选择，尽管目前还没有商业化的产品。我们之前根据两种抗甲真菌药物的性质以及其他贴片成分的性质，确定了两种最佳的指甲贴片配方。在本文中，我们的目的是进一步研究贴片配方作为局部指甲药物的潜力，特别是药物-粘合剂贴片释放的药物是否渗透到指甲板中并表现出抗真菌功效，以及它们在体内测试时是否以及在何种程度上在 2 周的时间内仍然附着在人指甲板上。此外，还确定了药物（盐酸阿莫罗芬、环吡酮胺）和 PSA（Duro-Tak 2852 或 Duro-Tak 202A）对这些参数的影响。我们发现，药物和 PSA 的性质都影响体外药物释放。药物的性质而不是 PSA 的性质影响亲水性药物通过人指甲屑的渗透，环吡酮胺（更小、疏水性更小的分子）的渗透要大得多（几乎是两倍）。体内驻留性，用 4 个贴片中的 3 个进行测试，不包括随着时间推移环吡酮胺降解的贴片，在脚趾甲上的驻留时间比手指甲长，这反映了它们在日常活动中指甲受到环境压力的影响要小得多。当贴片切割成指甲形状、在睡前使用以及在贴片顶部涂上透明无色指甲油以“密封”贴片在指甲上时，体内驻留性得到增强。贴片之间的比较表明，含有 Duro-Tak 202A 的贴片比含有 Duro-Tak 2852 的贴片具有更高的驻留性。与含有 Duro-Tak 2852 的贴片相比，Duro-Tak 202A 中含有的盐酸阿莫罗芬也显示出抗真菌功效，对于进一步开发作为潜在的脚趾甲药物特别有前途，至少两周内仍几乎完全附着在脚趾甲上。
