Novel drug-loaded patches for the treatment of nail diseases

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.

Ultimately, the research output will benefit patients suffering from a range of nail diseases, and their healthcare practitioners and providers. In the shorter term, the research will benefit the researchers involved, and other academic and industrial researchers working on nail diseases or in related fields for example, those formulating skin patches or even in quite unrelated fields (e.g. non-medical adhesion). It is expected that our basic research into nail patches will be exploited by the UK's pharmaceutical industry to develop medical nail patches. The latter are not commercially available, and the opportunity to market a first of its kind will increase the UK's economic competitiveness. If such patches could be developed from existing drugs and components such as adhesives that have already been tested for example, for toxicity, the first nail patches could be on the market within 6-7 years of the end of our research. Development of nail patches will provide patients with an effective, convenient, comfortable, user-friendly and non-invasive medicine. In some disorders, for example nail psoriasis (which is treated with repeated injections), the nail patch will greatly improve the patients' quality of life, and eliminate needle-stick injuries to healthcare professionals. In other disorders, such as fungal infections, where existing therapy suffers from toxicity/low efficacy, use of the patch as an adjunct will increase treatment efficacy and reduce the related adverse effects and costs to patients and healthcare providers. Thus our research will improve the nation's health and wealth. This multi-disciplinary project will provide immediate benefit to the researchers involved, enabling them to gain insights into the different fields of engineering and pharmacy, and to communicate and collaborate effectively within and outside their areas of expertise to advance their work. These portable skills will enhance the researchers' employability and their ability to discipline-hop. Following publication (within 5 years of the project's initiation), the work could be used by other researchers working in the nail and related or unrelated fields. Basic knowledge about the nail, for example, its surface energy, and methods developed during this project, such as, modelling in formulation and of patch adhesion to the nail, could be used by others in the nail, drug delivery (to other parts of the body) and other non-medical fields such as adhesion. Wide dissemination of the research via presentations at conferences and publication in journals will enable the use of this work by researchers in diverse fields. To enable commercial exploitation, the relevant intellectual property will be patented jointly by The School of Pharmacy and Imperial College; these institutions have considerable experience in the translation of their research. Subsequently, industrial partners will be sought via presentations at large and specialist scientific meetings such as the Controlled Release Society International meeting and the Skin Forum respectively, and at industry-academia networking events organised by bodies such as bioProcess UK and London Technology Network (LTN). SM is a Business Fellow contracted by the LTN to increase industry-academia interactions; her role will be exploited to seek industrial partners. Once intellectual property protection is secured, peer reviewed publications in high impact factor journals will be pursued and such publications will be mailed to our considerable contacts in pharmaceutical companies specialising in nail products, e.g. Almirall Hermal, Charles River, MedPharm. SM's laboratory has been funded by a number of companies developing topical medicines for the nail, as well as by GlaxoSmithKline and AstraZeneca. Funding (of up to 50,000) will also be sought from University College London Hospitals' (a partner of The School of Pharmacy) Therapeutic Innovation Fund for research translation.