Controlled Delivery of Therapeutics from Medical Implants
Lead Research Organisation:
University of Glasgow
Department Name: School of Engineering
Abstract
Typical therapeutic implants include devices such as stents, contact lenses and transdermal patches, where the therapeutic is usually contained in a biodegradable polymer coating or
contained within some nano-porous material attached to the main structure of the implant [1]. The particular therapeutic needed for a given application varies from, for example, antiinflammatory
drugs in drug-eluting stents, to antibiotics and growth factors to improve healing in orthopaedic applications [2]. These implants allow for localised treatment of a
condition, allowing for the dose of the therapeutic to be increased, but without adversely affecting the rest of the surrounding tissue or the whole body compared to pills and tablets
administered orally. One of the main advantages is the controlled release rate, meaning that the correct dose can be administered for long periods of time with one implant. The release
rate of the therapeutic is required to be controlled as for example, in the case of certain drugs, if we have a release rate which is too high, then toxic levels of the drug could be in
the bloodstream/tissue and if it is too low, then there would be no beneficial effect from the drug [1].
Despite the circumstance where the right type of therapeutic to be administered is known, the success of the therapeutic-releasing implant is greatly reliant on the release kinetics and
the subsequent transport of the therapeutic within the environment surrounding the implant. With regards to this, a mathematical and computational modelling approach will provide
valuable tools and therefore insight into how these processes, when combined, affect the success of the implant and so will aid in the development of optimisation strategies for
controlled, targeted delivery of the therapeutic.
Aims
This project will develop mathematical and computational models of the release of therapeutics from medical implants and the subsequent transport in the biological
surroundings. These models will be used to identify the dominant mechanisms governing the transport, and to help inform the design of superior devices.
Objectives
i. Review the literature and identify a subset of implants and applications where new mathematical modelling approaches are needed most
ii. Develop mathematical models of the release of the therapeutics under controlled conditions
iii. Validate the models against experimental data from the literature and/or from interaction with collaborators
iv. Develop mathematical models of the transport and behaviour of the therapeutic(s) in its(their) in-vivo environment(s)
v. Use the mathematical models to provide guidance on the optimal design of the
implant(s) considered
contained within some nano-porous material attached to the main structure of the implant [1]. The particular therapeutic needed for a given application varies from, for example, antiinflammatory
drugs in drug-eluting stents, to antibiotics and growth factors to improve healing in orthopaedic applications [2]. These implants allow for localised treatment of a
condition, allowing for the dose of the therapeutic to be increased, but without adversely affecting the rest of the surrounding tissue or the whole body compared to pills and tablets
administered orally. One of the main advantages is the controlled release rate, meaning that the correct dose can be administered for long periods of time with one implant. The release
rate of the therapeutic is required to be controlled as for example, in the case of certain drugs, if we have a release rate which is too high, then toxic levels of the drug could be in
the bloodstream/tissue and if it is too low, then there would be no beneficial effect from the drug [1].
Despite the circumstance where the right type of therapeutic to be administered is known, the success of the therapeutic-releasing implant is greatly reliant on the release kinetics and
the subsequent transport of the therapeutic within the environment surrounding the implant. With regards to this, a mathematical and computational modelling approach will provide
valuable tools and therefore insight into how these processes, when combined, affect the success of the implant and so will aid in the development of optimisation strategies for
controlled, targeted delivery of the therapeutic.
Aims
This project will develop mathematical and computational models of the release of therapeutics from medical implants and the subsequent transport in the biological
surroundings. These models will be used to identify the dominant mechanisms governing the transport, and to help inform the design of superior devices.
Objectives
i. Review the literature and identify a subset of implants and applications where new mathematical modelling approaches are needed most
ii. Develop mathematical models of the release of the therapeutics under controlled conditions
iii. Validate the models against experimental data from the literature and/or from interaction with collaborators
iv. Develop mathematical models of the transport and behaviour of the therapeutic(s) in its(their) in-vivo environment(s)
v. Use the mathematical models to provide guidance on the optimal design of the
implant(s) considered
Organisations
People |
ORCID iD |
| Jane Townson (Primary Supervisor) | |
| David King (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/N509668/1 | 01/10/2016 | 30/09/2021 | |||
| 1681205 | Studentship | EP/N509668/1 | 01/01/2016 | 01/11/2019 | David King |
| Description | 2017 UKICRS Workshop & Symposium, University of Strathclyde, UK |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other audiences |
| Results and Impact | The UKICRS 2017 conference was a chance for me to view the latest research in the field of controlled drug delivery. There were many presentations covering the latest experimental work from research groups from universities across the country, also present were a variety of industry representatives, who showcased some of their own work and up-to-date lab equipment in the form of presentations and stalls, where we could speak to them and view live demonstrations of equipment. My input was vastly different from the purely experimental work of other attendees, my presentation was entitled "Mathematical modelling of controlled antibiotic release from prototype orthopaedic fixation pins". In my presentation I showed the audience the latest stage my own research was at and showed a variety of different findings, for example, the significant influence stirring has in experimental setups and the need for accurate mathematical representations of device geometry. Although I was the only person present that used mathematics at the entire conference, my work generated discussion between myself and some experimentalists, some of which were interested in my modelling approach and others found themselves drawn to the area of drug release from orthopaedic implants. Overall, I believe that the conference was successful as I came away with greater knowledge of how the research in the field of drug release was going and how exactly experiments were being carried out and what equipment was used. |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.ukicrs.org/2017-symposium.html |
| Description | Mathematics for Industry PhD Modelling Week, University of Glasgow, UK |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | The modelling week was an ideal event to combine training, collaboration and communication between students of varied backgrounds, and to enhance problem solving skills within a student-orientated environment. Industrialists and clinicians helped fellow students develop awareness of the real-world applications of their work in one of the following modelling problems: the heart, drug discovery and medical devices. In the heart problem, it was noted that soft tissue mechanics play an essential role in all current models of the heart and one of the key issues is that the material parameters required for modelling cannot be directly obtained and these have to be inferred from medical images. This inverse approach uses combined mechanistic models and statistical parameter inference and students who participated in this problem gained insight by developing some of the approaches necessary in exploring simplified but relevant problems. In the drug discovery problem, it was noted that GlaxoSmithKline (GSK) is engaged in drug discovery research programmes. As well as experimental work, GSK adopt mathematical modelling and simulation to aid their understanding of what they observe in experiments and to make predictions on the effect of changes to their experiments. For any significant progress in this area to arise, an adequate description of the interaction between proteins and molecules is required. The students who worked on this problem used mathematics to model binding and diffusion processes in a number of relevant scenarios. For the medical devices problem, which is the one I worked on, given my current research, we were introduced to some of the current medical devices in use and orthopaedic implants, in particular, were the topic of discussion. Despite the many improvements over the years, there remain a number of challenges including the development of infection, inflammation and pain associated with orthopaedic implant use. It has been suggested that the local delivery of drug from the implant may be an ideal way of tackling some of these issues. In this problem, myself and the fellow students, developed models of some drug-releasing orthopaedic implants. This allowed us to identify the key parameters controlling the release and to potentially make suggestions about how the devices should be designed to control the release. |
| Year(s) Of Engagement Activity | 2016 |
| Description | Modelling and experiments in drug delivery systems (MEDDS) 2016 Conference at the University of Coimbra, Portugal |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | My supervisor and I attended this conference as it was highly applicable to my research funded by the award and also to my supervisor's work. He and I both gave presentations to the audience, at the University of Coimbra, Portugal, which was my first conference attendance. The event was centred on the experimental and mathematical modelling work within the field of drug delivery from medical implants and the activity allowed young academics and those with a firm foothold in the area to share their research and have a chance to network with others. The presentations generated ideas for further work, potential collaborations and sparked discussions over coffee breaks. My talk showcased what I had learned in the first 6 months of my PhD, which began in January of 2016 and the conference was held from 20-22 June 2016. In particular, I presented what was the latest experimental work in the field of drug delivery from orthopaedic implants and the initial attempts at mathematically describing these experiments. Overall, I consider the conference to be successful as I received positive feedback for my presentation from audience members and they noted their interest in the field and of course it stimulated my eagerness to learn more about my field of research. |
| Year(s) Of Engagement Activity | 2016 |
| URL | https://www.uc.pt/en/congressos/medds2016 |