Peptide-like hydrogels as long-acting injectable drug delivery platforms for the prevention of tuberculosis

About the Project

Provide a brief description of the project

Low to middle-income countries (LMIC) account for 95% of tuberculosis infections and deaths. Tuberculosis is currently the second highest infectious killer worldwide, after Covid-19, and is responsible for more deaths than HIV/AIDS. There is an urgent need for new convenient drug delivery systems to combat global health challenges in infectious disease, including tuberculosis. In this project, the aim to develop a long-acting preventative strategy to deliver single or multiple tuberculosis drugs within one injectable hydrogel depot. This strategy should eliminate pill fatigue encountered with existing oral therapies, enable better access to multiple drugs for a longer duration and be simple to administer in LMIC environments. To achieve this we will use a promising peptide-like, peptoid-peptide system, which we recently published in the top Chemistry journal, the Journal of the American Chemical Society. This platform has proven to form a drug-releasing hydrogel implant in situ in response to enzymes present in the subcutaneous skin space. The objective is to select the most promising peptoid-peptide formulation and demonstrate in vivo practicality for at least 84-day drug delivery. This selection will be made by characterising the mechanical (rheology), structural (microscopy, spectroscopy, neutron scattering at large scale facilities), biocompatibility (toxicity, immune response) and stability profiles for each formulation and establishing their relationship to drug release in vitro.

Training that will be provided through the research project

As a member of the Russell Group, Queen's University Belfast, which is consistently recognised as one of the leading universities for knowledge exchange in the UK, thus ensuring research is creating jobs, wealth, skills and innovation. The projects lead investigator Dr Laverty is a PhD graduate from the School of Pharmacy and has first-hand knowledge experience of the successful pathway a PhD from Queens University Belfast can provide. For this studentship the student will be trained in the following generic skills; developing writing skills, developing presentation skills, power point for academic presentations and posters, communication skills, introduction to research design, academic plagiarism, basic and advanced statistics, networking and negotiating, lab demonstrating and introduction to ref works. Students are also encouraged to use the Personal Development Planning (PDP) process to build a portfolio on learning, performance and achievement. PDP encourages the students to adopt a good work practice and supports the timely submission of thesis.

The student will receive formal training in the following specialist skills necessary for this project; peptide and peptoid synthesis, drug release protocols, confocal microscopy, scanning and transmission electron microscopy, tissue culture, HPLC, Fourier Transform infra-red spectrometry, circular dichroism, Mass Spectroscopy, NMR, neutron scattering techniques and use of in vivo facilities. The combination of these skills is highly transferable and should give the student a distinct advantage in the employment sector.

Expected impact activities

Healthcare Professionals/Regulators– This project will result in a novel drug delivery system that will serve as a superior alternative to existing formulations for healthcare professionals. The student will engage with individual consultants/physicians and drug regulators, providing knowledge input relating to clinical experimental design and result interpretation. We recognise it is important to instil healthcare practitioner confidence in the technology and obtain their feedback early in development.

Patients– The student will also engage with charities to provide stakeholder engagement activities (patient questionnaires, focus groups). We will explore: patient related factors; in-depth views on experiences and gauge their opinion on current treatments and our peptide-based platform.

• Involved in development of intellectual property
• Attendance at relevant conferences
• Engagement with industry
• Visits to large-scale neutron scattering facilities
• Generation of publications

Funding Notes

This project is not funded; applications are welcome from self-funding candidates.

References

Hydrogel; drug delivery; formulation; long-acting injectable; peptides; tuberculosis