Dataset for "Enzyme triggered L-α/D-peptide hydrogels as a long-acting injectable delivery platform for HIV/AIDS"

Dataset for "Enzyme triggered L-α/D-peptide hydrogels as a long-acting injectable delivery platform for HIV/AIDS".

Data relates to a formulation composed of a self-assembling ultrashort D or L peptide hydrogelator, namely phosphorylated (naphthalene-2-ly)-acetyl-diphenylalanine-lysine-tyrosine-OH (NapFFKY[p]-OH), to which zidovudine is conjugated covalently . Data includes rheological analysis, small angle neutron scattering, resistance to protease degradation (biostability), cell toxicity and drug release (both in vitro and in vivo).

Paper abstract: Eradicating HIV/AIDS by 2030 is a central goal of the World Health Organization. Key to addressing this challenge is overcoming issues patients have with adhering to their medicines. This includes a commitment to complicated drug dosage regimens, for example a daily intake of tablets at very specific times. There is a clear need for a convenient and effective long-acting formulation to deliver drugs to patients over a sustained period. This paper aims to develop an injectable in situ forming hydrogel implant for the delivery of a model HIV/AIDS antiretroviral drug (zidovudine) over 28 days. The formulation is composed of a self-assembling ultrashort D or L- peptide hydrogelator, namely phosphorylated (naphthalene-2-ly)-acetyl-diphenylalanine-lysine-tyrosine-OH (NapFFKY[p]-OH), to which zidovudine is conjugated covalently via an ester linkage. This platform is formulated as a powder that can be readily dissolved in aqueous buffer to form an injectable antiretroviral-peptide solution. Using rheological analysis, peptides demonstrated enzyme instructed self-assembly, forming hydrogels within minutes in the presence of phosphatase enzyme. Small angle neutron scattering suggest peptide gels form fibres of narrow radius (~2 nm) and large length, closely fitting the flexible cylinder elliptical model. D-peptides were particularly promising as a long-acting drug delivery platform, displaying resistance to protease degradation for 28 days. Drug release, via hydrolysis of the drug-peptide ester linkage, was shown to progress under physiological conditions (37 C, pH 7.4, H2O). In vivo studies in Sprague Dawley rats demonstrated zidovudine blood plasma concentrations to be within IC50 range (30 – 130 ng/mL) for 35 days after subcutaneous administration of Napffk(AZT)Y[p]G-OH. This work is a proof-of-concept for the development of a long-acting combined injectable in situ forming implant using a peptide hydrogel formulation strategy. A successful single, long-acting, highly user-adherent product that targets HIV/AIDS is a high priority due to the positive societal, health and economic impact this technology would provide.