Understanding microscopic properties and drug diffusion kinetics in a long-acting peptide hydrogel drug delivery implant for combined contraception and HIV prevention.

There is a major need for a single effective platform to delivery both HIV/AIDS and contraceptive drugs over a prolonged period e.g. 28 days We are developing a hydrogel implant, composed of biologically stable peptide-like molecules termed peptoid-D-peptides, that form gels in response to enzymes present within the skin. Patients struggle to adhere to complex regimens of these medicines, which require a cocktail of drugs to be taken several times daily. Our therapy removes this need, improving adherence to medication and reducing mother to foetal HIV transmission. This project will explore the role of gel fibre structure and entangled gel fibre networks on both i) mechanical (gel formation, rheology, gel strength) and ii) drug release properties (drug cleavage from peptoid-D-peptide, drug diffusion). Small angle neutron scattering will be used to probe the properties of gel fibres in the presence of multiple HIV/AIDS and contraceptive drugs. This will provide SANS data that will be valuable in optimising the peptoid-D-peptide’s chemical structure and formulation parameters for 28 day combined delivery of HIV/AIDs and contraceptive drugs within one injectable product.

目前亟需一种单一有效的平台，能够在较长周期（例如28天）内递送HIV/AIDS药物与避孕药物。我们正在开发一种水凝胶植入物，其由生物稳定性类肽分子构成——这类分子被称为拟肽-D-肽（peptoid-D-peptides），可响应皮肤内存在的酶形成凝胶。患者难以遵循这些药物的复杂治疗方案，此类方案要求每日多次服用混合药物。我们的疗法消除了这一需求，可提高药物依从性并减少HIV的母婴传播。本项目将探究凝胶纤维结构及缠结凝胶纤维网络在以下两方面的作用：i) 力学特性（凝胶形成、流变学、凝胶强度）；ii) 药物释放特性（拟肽-D-肽的药物裂解、药物扩散）。小角中子散射（Small Angle Neutron Scattering，SANS）将用于探测多种HIV/AIDS药物与避孕药物存在时凝胶纤维的特性。这将提供SANS数据，对优化拟肽-D-肽的化学结构及配方参数具有重要价值，从而实现28天内通过单一注射产品联合递送HIV/AIDS药物与避孕药物。