In the future, 3-D printed drug delivery devices will allow for patient-specific formulation and tailored release characteristics. However, there are still many obstacles to overcome.
It is beginning to be recognised that disease is personal and genotypical and as such, future advances in treatment will rely on multimodal approaches, tailored specifically to the patient. This requires a longitudinal methodology encompassing diagnosis, therapy and monitoring.
3D printing has a role to play in all of these aspects, but most explicitly in the development of platforms for personalised, bespoke drug delivery. Current forms of treatment are in general, bolus, with a systemic flooding of the system (e.g., ingesting of a tablet). 3D printed drug delivery systems, however, present the opportunity for tailored formulation, whereby the release strategy can be embodied at the design state, with the geometry and material functionality specifically tailored to achieve the desired release characteristics. This is a tremendously attractive proposition – imagine being able to present to your attending physician, be assessed, and have a treatment and its delivery platform designed and manufactured specifically for you.
The route to this goal, however, is complex and not without challenge. Diagnostic capability needs to be matched to manufacturing. In order to design such specific platforms, an intimate understanding of the material’s structural, degradation and dissolution mechanics and chemistry is required, and the ability to manufacture, with precision and repeatability is paramount. Advanced materials, both design and manufacture, are a key challenge for personalised 3D printing. The current understanding of how one can fine tune the functionalization of molecule is far from complete – one is not able usually to “dial up” the molecule or material that you need for a specific purpose. Manufacture of such bespoke chemistries, on demand, is not possible with current techniques.
|Professor Ricky Wildman, University of Nottingham|
Progress on this is being made at the University of Nottingham. A collaboration between the Faculty of Engineering and the School of Pharmacy is developing a new range of biocompatible, ink jettable biomaterials, primarily for the purpose of drug delivery. These efforts take advantage of the state of the art facilities at the EPSRC Centre for Innovative Manufacturing in Additive Manufacturing and in the Laboratory of Biophysics and Surface Analysis. Within this laboratory there is a production line of materials developing, printing development, novel process assessment and object printing. Here we imagine the possibility of combining multifunctional materials for biomaterials applications – the combining of circuitry with structural material for sensors, combining drug and support for drug delivery and API and excipient for dosage applications. The ability to combine materials on the fly, gives the possibility not only of multimaterial, multifunctional objects, but the grading and tuning of material, such as the active pharmaceutical ingredient (API), such that we can select and produce personalised delivery rates for multidrug/modal systems.
There are a number of challenges with this approach. The materials that are to be used need to be liquid, but curable and retain their biorelevant function. Currently, there is a limited palette of available materials for this purpose. Printing of such materials is in its early days and reliable, precise deposition is only beginning to be understood. Further, 3D printing often requires the use of support structures that must be eliminated post printing. One would ideally like to remove the need for supports, but if necessary, supports will need to be removable via a nontoxic process, leave no residue that would affect the functional structure and equally importantly, not add significantly to the cost of the product.
These challenges are being overcome though, through the combination of fundamental understanding and industrial collaboration. For example, at Nottingham, the printing of solid dosage forms and the printing of multifunctional 3D objects demonstrated, pointing to 3D printing in the near future, creating the opportunity for patient specific treatment, within the environment of the clinical lab. In combination with the practical issues of printing, a fundamental understanding of polymer degradation and characterisation of new materials, both prior and post printing is needed to obtain control over the process. Underpinning this is a need for new design methods that can automatically seek out the geometries required, and the distributions of material to affect the drug release rate that is required.
In future, the mechanism of treatment will be inverted, with clinician feeding the diagnosis and treatment requirements to a manufacturing suite, who will dial up the materials required and the structure needed to deliver the perfect, treatment profile, ready to printed locally and near to point of care. Through the combined efforts of science, industry and regulatory authorities we will see this realised in our lifetime.