Novel drug-loaded patches for the treatment of nail diseases

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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.