Functionalised silicone elastomers for drug delivery

It is increasingly acknowledged that drug delivery is a key factor in developing new medicines, and that new polymeric biomaterials will play a critical role in driving innovation. In 1964, researchers first demonstrated that small molecules – including certain dyes and drugs – were able to diffuse slowly from silicone elastomer capsules implanted in animals. Silicone elastomers have since been exploited for a myriad of controlled release drug delivery applications, including intrauterine devices, vaginal rings, subdermal implants and other devices for contraception, estrogen replacement therapy, HIV prevention, and treatment of bladder cancer and eye diseases. However, to date, all marketed drug delivery products containing silicone elastomers are fabricated from a single silicone chemistry—referred to as polydimethylsiloxane—in which the silicone polymer is functionalised only with methyl groups. Surprisingly, although silicone elastomers having other functional groups are well-established in the medical device, electronics and aerospace industries, they have not been extensively investigated or exploited for use in drug delivery applications. In this project, for the first time, we will assess the potential for controlled drug release from chemically functionalised silicone elastomers. Specifically, working in partnership with NuSil—a global leader in the synthesis, formulation and supply of silicone excipients for medical and drug delivery applications—the aim of this project is to assess the release of model drugs from silicone polymers/elastomers containing methyl, phenyl, trifluoropropyl and custom hydrophilic groups (Fig. 1).

Fig. 1. Some of the silicone polymers/elastomers for testing as part of this PhD project.

 

The objectives of the project are:   

1. To characterise the supplied silicone polymers (containing methyl, phenyl, trifluoropropyl and custom hydrophilic moieties) using various analytical techniques (including NMR spectroscopy, infrared spectroscopy, differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), oscillatory rheology, etc.)
2. To measure the solubility characteristics of model drugs (e.g., dapivirine, metronidazole and gemcitabine) in the silicone polymers
3. To assess the isothermal cure characteristics of the various silicone elastomers using DSC, both without and with inclusion of model drugs
4. To test in vitro release of model drugs from the various silicone elastomers, and to model the release data to obtain drug diffusion coefficients, drug permeation coefficients, release rates, lag/burst times, etc.
5. To assess the extent of swelling of the silicone elastomers when immersed in simulated biological media
6. To assess the mechanical properties of devices fabricated from the various silicone elastomers
7. To assess the potential for combining the multiple silicone elastomer types within reservoir-type devices for further modulation/control of drug release rates

About Professor Karl Malcolm

I am a world-leading academic researcher with extensive practical and commercial knowledge/expertise in developing controlled release drug delivery products, most notably for use in women’s sexual and reproductive health. For example, the antiretroviral-releasing silicone elastomer vaginal ring product I conceived and helped develop over the past twenty years is now being used by women across Africa for prevention of sexually-acquired HIV infection. In fact, most of the 100+ research articles I have published over the past 25 years have focused on silicone elastomer materials. This project affords a unique opportunity for partnership between a world-leading academic and a world-leading silicone manufacturing/supply company to advance new innovations in the drug delivery field.

Briefly, to be eligible for this CAST award, a candidate must satisfy ALL THREE eligibility criteria below.

Residency criteria

The candidate must be ordinarily resident in the UK or Islands, including the Channel

Islands and Isle of Man, for the full three year period before the first day of the first

academic year of the course, i.e. normally 1 October. For Non-EU nationals, the main purpose of residence in the UK must NOT have been to receive full time education during any part of that three-year period. If you have more complex residency status, please refer to the link below.

 

Nationality criteria

The candidate must be a UK national, an Irish national; or an EU national or relevant family member of an EU national with ‘protected rights’ under the EU Withdrawal Agreement with pre-settled or settled status under the EU Settlement Scheme. If you have more complex nationality status, please refer to the link below.

Academic criteria

The required academic qualification is a first or high upper second-class honours degree from a university in the United Kingdom or Ireland, or qualifications and experience considered by the University as equivalent to this standard. Candidates must have official, final results of all qualifications to be used to meet the

academic requirements before the start of the Studentship.

Full terms and conditions around the criteria for CAST awards are provided at the link below:

https://www.economy-ni.gov.uk/sites/default/files/publications/economy/Postgraduate-Studentships-Terms-Conditions-2023-24.pdf

All applications must be submitted via the link provided below. If this is your first application for postgraduate study at Queen’s University Belfast, there is an option to register on the platform. 

https://dap.qub.ac.uk/portal/user/u_login.php

Please note that applicants do not need to draft a detailed research proposal. Instead, applicants can simply copy and paste the summary descriptive text provided above. However, you may wish to elaborate further on the concept, particularly if you have other ideas around the project topic.

If you require further information, please contact Prof. Karl Malcolm directly (k.malcolm@qub.ac.uk)

The project will provide extensive training and skills development for the student in the following topics:

·      drug formulation and testing

·      injection molding

·      drug quantification using high performance liquid chromatography (HPLC)

·      in vitro drug release testing

·      use of analytical methods, e.g., NMR, FT-IR, DSC, TGA, rheological and mechanical testing methods

·      planning and organising skills: designing and planning of experiments

·      numeracy and statistical skills

·      teamwork skills: working confidently as part of a large research team