Injectable sustained-release hydrogel for high-concentration antibody delivery
Name
d4pm00290c.pdf
Description
Published version
Size
1.31 MB
Format
Adobe PDF
Checksum (MD5)
d8cd7a71c5d971548571b7b217504388
Author(s)
Zheng, Talia
Doyle, Patrick S
Date Issued
January 21, 2025
Journal
RSC Pharmaceutics
Publisher
Royal Society of Chemistry
Citation
Zheng, Talia and Doyle, Patrick S. 2025. "Injectable sustained-release hydrogel for high-concentration antibody delivery." RSC Pharmaceutics, 2 (1).
Version
Final published version
Abstract
There is an increasing interest in subcutaneous (SC) delivery as an alternative to the traditional intravenous (IV) for immunotherapies and other advanced therapies. High-concentration formulations of antibodies are needed to meet the limited-volume requirements of subcutaneous SC delivery. Despite this need, there remain challenges in delivering stable and injectable antibodies in these high concentrations. Hydrogel encapsulation of amorphous solid antibodies has been proven to improve the stability and injectability of high-concentration antibody formulations. However, the antibody is quickly released from the hydrogel due to the material's porosity, leading to rapid, uncontrolled drug release kinetics undesirable for the drug's efficacy and safety. In this paper, we propose a dual-network composite hydrogel which leverages interactions between the two polymer networks to achieve controlled release of the antibody. We load the solid form of the antibody at high concentrations within alginate hydrogel microparticles which are then suspended in thermogelling methylcellulose solution to formulate the in situ gelling composite hydrogel. By facile chemical modification of the alginate to tune the microparticles’ gel properties and alginate–methylcellulose interactions, we demonstrate how the composite system can delay release of the drug in a tunable manner and achieve a near-zero order release profile for improved therapeutic efficacy. We show acceptable injectability properties of the composite hydrogel at high antibody concentrations, highlighting the functionalities of dualnetwork encapsulation. We imagine this composite system to be applicable for the sustained delivery of various therapeutic protein forms, especially for high-loading SC formulations.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
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Creative Commons Attribution-Noncommercial-ShareAlike
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DOI of Published Version
https://doi.org/10.1039/d4pm00290c
