Unravelling microscopic properties of long-acting peptide hydrogel HIV/AIDS drug delivery implants using Small Angle Neutron Scattering (SANS)

Introduction: Eradicating HIV/AIDS by 2030 is a central goal of the World Health Organization [1]. However, low patient compliance with current treatments due to complex drug dosing presents a significant challenge. To address this, we propose a simple, longacting formulation based on an enzyme-responsive peptide hydrogelator, namely phosphorylated (naphthalene-2-ly)-acetyl-diphenylalanine-lysine-tyrosine-OH (NapFFKY[p]-OH), conjugated with zidovudine, forming an injectable platform. Methods: SANS was employed with the D11 instrument at the Institute Laue-Langevin, oscillatory rheology tests, scanning and transmission electron microscopy, circular dichroism, in vitro drug release assays, and in vivo experiments involving subcutaneous injection in rats. Results: SANS analysis revealed that the gel fibre radius of various peptide hydrogel formulations matched predictions of the flexible cylinder elliptical model. Entangled gel fibres contributed to stiffness and strength, regulated by external conditions. Peptide gels with the drug exhibited lower stiffness than those without. SANS analysis confirmed the formation of entangled gel fibres with a narrow radius (~2 nm) and substantial length, commonly observed in such systems [2]. Subcutaneous injection of Napffk(AZT)Y[p]G-OH in Sprague Dawley rats demonstrated zidovudine blood plasma concentrations within the half maximal inhibitory concentration (IC50) range (30–130 ng mL−1) for 35 days. Conclusion: Our research proposes a long-acting injectable drug delivery strategy using peptide-based hydrogels as a water-based formulation. SANS analysis provides crucial insights into the network structure, enabling tailoring of properties for sustained drug delivery. This platform is a proof-of-concept for a HIV/AIDS therapy with a simplified dosing regimen injection to enhance patient adherence to medicines. References: [1] The AIDS response in the 2030 agenda for sustainable development: joint work, shared gains | UNAIDS. https://www.unaids.org/en/AIDS_SDGs. [2] E. R. Cross, S. Sproules, R. Schweins, E. R. Draper, D. J. Adams, J. Am. Chem. Soc. 2018, 140, 8667.Acknowledgements: This work was supported by a grant from the Engineering and Physical Sciences Research Council (EPSRC) and Medical Research Council (MRC). Presenter Biography: Yuming An is a PhD candidate at the School of Pharmacy, Queen’s University Belfast. He carries out research in the fields of peptide science and drug delivery. Learning Objectives Understanding hydrogels’ macroscopic properties and their impact on zidovudine release. Utilized SANS, rheology, and drug release assays as primary techniques.Improved understanding of gel structure and drug delivery for HIV/AIDS treatment.