A Portable Electrohydrodynamic Device for in-situ Production of Multi-Layered Drug-Loaded Meshes

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The proposed research describes a novel engineering approach to point-of-need delivery of controlled release medications for wound and burn treatment, based on an innovative portable device which allows in situ generation of nano-/micro fibrous meshes. These fibres can contain multiple layers of active pharmaceutical ingredients (APIs) in a core-shell configuration (potentially up to at least four layers), allowing compartmentalisation of agents ranging from proteins to low molecular weight antibiotics and including innovative therapeutic oligosaccharides. Nano- and microfibres with compartmentalised structures are currently attracting a great deal of interest within the drug delivery arena due to the advantages of high surface area, high fluid permeation, ready separation of incompatible drugs into physically distinct environments, the ability to tune drug release rates via incorporation into controlled release polymers and the physical flexibility and versatility of the macroscopic mesh structure. Furthermore, given recent emphasis on combination therapies, the possibility of generating compartmentalised systems using, for example, coaxial and multi-axial electrohydrodynamic (EHD) technology is highly attractive. One example of such an application is the treatment of wounds and burns, whereby the flexibility of shape of the meshes to neatly fill the lesion, the high fluid permeation of the mesh facilitating tissue regrowth, the tunable release of therapeutic agents and the biodegradation of the mesh are all perfectly feasible attributes that would render a drug-loaded nanofibre approach highly advantageous. A further possibility, not yet realised in practice, is the generation of micro/nanofibres in situ at the point of trauma. Were this to be possible, then valuable time to treatment would be saved as agents designed to stop bleeding, prevent infection, reduce pain or promote healing could be administered quickly in a form which could be applied to a wide range of lesion architectures and areas. Indeed, a portable system could also be used in conflict situations, for patients with mobility difficulties being treated at home for conditions such as diabetic ulcer or for otherwise medically inaccessible regions such as refugee camps, while the use of biodegradable polymer bases would allow the mesh to simply be resorbed over a period of time without damage to the lesion associated with dressing removal. Moreover, the capability to generate highly permeable microfibrous meshes at point-of-need enables an alternative nasal route for sustained and controlled drug release when oral/intravenous drug delivery is rendered impractical during emergencies where the patient may be unconscious with poor vein access (e.g. heroin overdose) or may even be having a seizure (e.g. status epilepticus). Overall, therefore, a 'field' system for simple and inexpensive administration of complex drug-loaded fibre meshes would have huge patient benefit for a wide range of conditions and would represent a significant breakthrough in engineering-led therapeutic development. Clearly, however, such a system would present a series of profound engineering challenges. Despite recent advances in fibre production technology, the generation of fibres with compartmentalised systems requires bulky, expensive (>£20k), bench-top high voltage supply and syringe pumps that are confined to a laboratory or factory environment. Developing a portable, hand-held, cheaper (<£2k), miniature EHD device that can generate multilayered therapeutic materials could revolutionise the practical applicability of micro/nanofibres. We believe, based on our work to date, that such an approach is now possible and the project outlined here, which focuses on the engineering issues associated with the development of our prototype device and the challenges of drug incorporation, would lay the foundation for the use of this approach in a wide range of therapeutic applications.