Issue 6, 2023

Subcutaneous delivery of an antibody against SARS-CoV-2 from a supramolecular hydrogel depot

Abstract

Prolonged maintenance of therapeutically-relevant levels of broadly neutralizing antibodies (bnAbs) is necessary to enable passive immunization against infectious disease. Unfortunately, protection only lasts for as long as these bnAbs remain present at a sufficiently high concentration in the body. Poor pharmacokinetics and burdensome administration are two challenges that need to be addressed in order to make pre- and post-exposure prophylaxis with bnAbs feasible and effective. In this work, we develop a supramolecular hydrogel as an injectable, subcutaneous depot to encapsulate and deliver antibody drug cargo. This polymer-nanoparticle (PNP) hydrogel exhibits shear-thinning and self-healing properties that are required for an injectable drug delivery vehicle. In vitro drug release assays and diffusion measurements indicate that the PNP hydrogels prevent burst release and slow the release of encapsulated antibodies. Delivery of bnAbs against SARS-CoV-2 from PNP hydrogels is compared to standard routes of administration in a preclinical mouse model. We develop a multi-compartment model to understand the ability of these subcutaneous depot materials to modulate the pharmacokinetics of released antibodies; the model is extrapolated to explore the requirements needed for novel materials to successfully deliver relevant antibody therapeutics with different pharmacokinetic characteristics.

Graphical abstract: Subcutaneous delivery of an antibody against SARS-CoV-2 from a supramolecular hydrogel depot

Supplementary files

Article information

Article type
Paper
Submitted
24 5 2022
Accepted
21 8 2022
First published
30 1 2023
This article is Open Access
Creative Commons BY-NC license

Biomater. Sci., 2023,11, 2065-2079

Subcutaneous delivery of an antibody against SARS-CoV-2 from a supramolecular hydrogel depot

C. M. Kasse, A. C. Yu, A. E. Powell, G. A. Roth, C. S. Liong, C. K. Jons, A. Buahin, C. L. Maikawa, X. Zhou, S. Youssef, J. E. Glanville and E. A. Appel, Biomater. Sci., 2023, 11, 2065 DOI: 10.1039/D2BM00819J

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