Enzyme-responsive peptide hydrogel as in situ forming long-acting drug delivery implants

   School of Pharmacy

   Applications accepted all year round  Self-Funded PhD Students Only

About the Project

One of the key issues in the treatment and prevention of disease is that patients struggle to adhere to the complex dosage regimens of therapies, which often require multiple dosing at very specific times each day. Recent strategies have focused on solving patient adherence issues by using long-acting injectable technologies. Our peptide platform has high potential to be adopted as a novel injectable implant for the sustained delivery of drugs for conditions where patients have difficulty adhering to their medicines (e.g. HIV/AIDS, contraception, Alzheimer’s, tuberculosis, depression, substance abuse, schizophrenia, malaria). Existing long-acting products have several significant issues that limit their wider use, such as:

- the use of water-insoluble drugs that limit the type of drugs that can be incorporated into the product

- fast drug release after insertion leading to potential toxicity issues/concerns over dose received

- a need for surgery for implant insertion and removal

- a requirement for large needles

- stability issues upon storage/transport which can result in clogging of syringes and incomplete dosing of drugs.

Our project aims to overcome these issues by creating a soluble injection of enhanced stability, for improved ease of administration under the skin. This will form a hydrogel implant in response to enzymes present within the skin to release drugs long-term, removing the need for daily dosing. Our injectable implant is composed of peptide-like molecules that are capable of forming tissue-like hydrogels, which can be tailored to gradually release drugs for at least 28 days. This will remove the need for patients to comply with complex drug dosing regimens on a daily basis and improve their adherence to medication.

Natural peptides form the building blocks of proteins and tissues. Their use as a drug releasing hydrogel implant for administration under the skin is promising due to their high biocompatibility, but limited by their rapid degradation within hours by enzymes present in the human body. This project overcomes stability issues by studying peptide-mimetics, which retain the positive properties of peptides (e.g. biocompatibility, easy drug attachment) with the ability to form hydrogels that will be stable for the duration of therapy. Peptide-mimetics can be tailored to degrade within the body over months into non-toxic components that are eliminated from the patient, meaning surgical removal is not necessary. Our peptide-mimetics possess high chemical versatility (i.e. wide choice of chemical functional groups). Therefore, multiple drugs can be attached directly to the peptide-mimetic hydrogel enabling large quantities of drug to be incorporated to meet in vivo therapeutic need for at least 28 days. Drug detachment proceeds in physiological conditions after the hydrogel forms reducing potential for rapid burst release of drug upon injection. Drug release studies will assess the potential for sustained drug administration in a bid to minimise pharmacokinetic peaks and troughs in drug concentrations. The peptide-mimetics studied in this project are purposefully small molecules that are cheap to manufacture, improving their potential to be clinically translated as a pharmaceutical product and effectively utilised within healthcare budgets for patient and societal benefit. The data obtained will allow the practical utility of this peptide-mimetic hydrogel approach to long-acting injectable administration of drugs to be assessed.

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 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 in vivo facilities. The combination of these skills is highly transferable and should give the student a distinct advantage in the employment sector.

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.

Home applicants must meet the following academic criteria:

1st or 2.1 honours degree in a relevant subject. Relevant subjects include Pharmacy, Pharmaceutical Sciences, Biochemistry, Biological/Biomedical Sciences, Chemistry, Engineering, or a closely related discipline.

International applicants must meet the following academic criteria:

IELTS (or equivalent) of 7.0, a 2.1 honours degree (or equivalent) and a master’s degree in a relevant subject.

Applicants should apply through the University's Direct Application Portal: https://dap.qub.ac.uk/portal/user/u_login.php

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