Abstract
This thesis reports the development of an enzyme-responsive peptoid-D-peptide hydrogel for the sustained delivery of antiretroviral and contraceptive agents as a multipurpose prevention technology (MPT) for women. The hydrogelator was synthesised via solid-phase peptide and peptoid chemistry, incorporating an alkaline phosphatase-sensitive phosphotyrosine residue and a drug-conjugation site on D-lysine. The antiretroviral drugs cabotegravir and MIV-150, and the contraceptive etonogestrel, were attached to the peptoid-D-peptide through succinate linkers comprising a hydrolysable drug–succinate ester and a succinate–lysine amide bond. The resulting conjugates were characterised by proton and phosphorus nuclear magnetic resonance spectroscopy, electrospray ionisation mass spectrometry, and reverse-phase high-performance liquid chromatography. Rheological studies demonstrated that the hydrogel rapidly formed in situ within 60 s and exhibited a storage modulus exceeding the loss modulus, confirming elastic-dominant gel behaviour and its ability to form a peptide-like hydrogel. In vitro drug-release studies conducted over 84 days revealed that hydrogels bearing drugs covalently attached through the succinate linkers exhibited significantly reduced burst release compared with physically mixed formulations. These findings demonstrate that this injectable peptide hydrogel provides a robust, long-acting platform for combined HIV prevention and contraception, representing a promising step towards female-controlled MPTs.Thesis is embargoed until 31 December 2031.
| Date of Award | Dec 2026 |
|---|---|
| Original language | English |
| Awarding Institution |
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| Sponsors | Engineering and Physical Sciences Research Council |
| Supervisor | Garry Laverty (Supervisor), Alejandro Paredes (Supervisor), Sreekanth Pentlavalli (Supervisor) & Sophie Coulter (Supervisor) |
Keywords
- Peptoid-D-peptide
- enzyme-responsive hydrogel
- sustained drug release
- controlled release
- multipurpose prevention technology
- hydrogels
- HIV Prevention
- contraception
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