Novel Peptoid Hydrogels as Long Acting Injectable Drug Delivery Systems (360G-Wellcome-207618_Z_17_Z)

Long-acting injectable (LAI) nanosuspensions comprising water-insoluble drugs are already widely marketed for treatment of schizophrenia and are presently being evaluated in late-stage clinical studies as formulation strategies for pre-exposure prophylaxis (PrEP) against HIV infection. Alternative formulations are needed to overcome some of the inherent disadvantages with nanosuspension injections, including the requirement for use of water-insoluble actives, the formation of amorphous drug during milling, and difficulties around manufacturing scale-up. This project will investigate for the first time the use of enzyme-responsive peptoid hydrogelators as a new technology platform for development of LAI medicines. Peptoids are biocompatible molecules that mimic naturally occurring peptides. They form structured, tissue-like, hydrogel networks in aqueous environments and can offer sustained release of drugs. Here, we aim to investigate the potential of novel peptoid hydrogels for long–acting subcutaneous drug administration. The formulations will comprise a peptoid backbone capable of hydrogelation; a phosphate group to increase aqueous solubility and whose enzymatic removal triggers hydrogel formation in vivo; and a model antiretroviral molecule attached via a physiologically hydrolysable group. The goals include: (i) characterisation of antiretroviral-conjugated peptoids for their ability to form hydrogels; (ii) testing the biocompatibility of peptoid hydrogels; and (iii) evaluation of sustained drug release properties.