Novel drug-loaded patches for the treatment of nail diseases

指甲疾病很常见，需要治疗。例如，指甲真菌感染，影响高达40%的人口，在老年人，免疫抑制和糖尿病患者中更常见，并可显着影响患者的生活质量。例如，走路是痛苦的，因为脚趾甲有病，难看的指甲会抑制社交和工作。真菌感染的主要治疗方案-口服抗真菌药物治疗-存在严重的缺点，如肝毒性。另一种常见的指甲疾病，牛皮癣，是通过反复和极其痛苦的药物注射到指甲周围的皮肤治疗。有效的局部治疗可以替代或补充目前的治疗，从而消除/减少口服/注射治疗的不良反应。不幸的是，现有的用于真菌感染的局部产品显示出有限的成功，并且没有局部产品被许可用于指甲银屑病。因此，研究指甲疾病的局部治疗对于解决这种未满足的临床需求至关重要。我们建议研究贴片作为药物载体用于局部治疗指甲疾病。在应用于指甲板之后，贴剂将保留在疾病部位并持续长时间释放药物。这种非侵入性的分娩方法预计将受到患者的欢迎。贴片已经可商购获得用于施加到皮肤上。然而，由于药物之间以及皮肤和指甲表面之间的差异，皮肤贴片不能简单地装载用于指甲疾病的药物。指甲贴片必须从头开始配制。我们的目的是开发一种方法，合理设计载药甲贴片。通过调查基础科学，并利用我们在工程，建模和药物输送方面的综合专业知识，以及我们两个机构的设施，我们将开发一种科学方法来制定指甲贴片，这将普遍适用于一系列疾病和药物。因此，拟议的工作是从根本上不同的稀缺文献中描述的指甲补丁，后者只被用作一个方便的车辆，或重要的补丁组件对补丁的疗效的影响进行了测试，以经验的方式。我们将使用理论、实验和建模方法的组合来：i）识别正确的贴剂组分，例如粘合剂、背衬膜、溶剂，ii）配制载药指甲贴剂，以及iii）评价配制的贴剂对指甲的粘附性、对指甲水合作用的影响、药物转移到指甲中以及随后对疾病的药物作用。溶解度参数、有限元分析和内聚区模型等理论概念将用于选择正确的参数，减少所需实验的数量，并最终提供一些现成的工具。对配制的贴剂对指甲疾病的功效的评估将表明所开发的方法的成功。为了能够测试贴片的功效，选择真菌感染作为指甲疾病，并且将在这项工作中使用抗真菌药物特比萘芬和阿莫罗芬。两种药物的使用将表明所开发方法的稳健性和普遍性。

Nail diseases are common and require treatment. For example, nail fungal infections, affect up to 40% of the population, are more common in the elderly, immunosuppressed and diabetics and can significantly affect the quality of life of sufferers. For example, walking is painful due to diseased toenails, and unsightly nails inhibit social interactions and work. The main treatment regimen for fungal infections - oral therapy with antifungals - suffers from serious drawbacks such as liver toxicity. Another common nail disease, psoriasis, is treated with repeated and extremely painful injections of the drug into the skin surrounding the nail. Effective topical therapy could replace or complement the current treatments and thereby lead to elimination/reduction of the adverse effects of oral/injected therapies. Unfortunately, the existing topical products for fungal infections have shown limited success, and no topical products have been licensed for nail psoriasis. Research into the topical therapy of nail diseases is therefore essential to address this unmet clinical need. We propose to investigate patches as drug carriers for the topical treatment of nail diseases. Following application to the nail plate, the patch would remain at the disease site and continuously release drug for long durations. This non-invasive method of delivery is expected to be popular with patients. Patches are already commercially available for application to the skin. However due to the differences between the drugs, and between the skin and the nail surfaces, skin patches cannot simply be loaded with drugs for nail diseases. Nail patches have to be formulated from scratch. Our aim is to develop a method for the rational design of drug-loaded nail patches. By investigating the underpinning science, and by exploiting our combined expertise in engineering, modelling, and drug delivery, and the facilities at our two institutions, we will develop a scientific method to formulate nail patches which will be universally applicable to a range of diseases and drugs. Thus, the proposed work is fundamentally different from those described in the scarce literature on nail patches, where the latter have only been used as a convenient vehicle, or where the influence of important patch components on patch efficacy was tested in an empirical manner. We will use a combination of theoretical, experimental and modelling methods to: i) identify the correct patch components, such as the adhesive, backing membrane, solvents, ii) formulate drug-loaded nail patches, and iii) evaluate the formulated patches in terms of adhesion to the nail plate, effects on nail plate hydration, drug transfer into the nail plate, and subsequent drug action against the disease. Theoretical concepts such as solubility parameter, and finite element analysis and cohesive zone models will be used to select the correct parameters, reduce the number of required experiments, and ultimately provide some ready-to-use tools. Assessment of the efficacy of the formulated patch against a nail disorder will indicate the success of the developed methodology. To enable the testing of patch efficacy, fungal infection is chosen as the nail disorder, and the anti-fungal drugs, terbinafine and amorolfine will be used in this work. Use of two drugs will give an indication of the robustness and universality of the developed methods.