Long-acting injectable antibody delivery system for chronic inflammation treatment

Overview

Chronic inflammatory conditions often require frequent injections of biologic drugs such as anti-TNF-alpha antibodies, which can burden patients and reduce adherence. This technology offers a long-acting delivery approach in which a therapeutic antibody is released slowly from an injectable depot over many months, potentially reducing dosing frequency and total antibody dose required for sustained therapeutic effect.

The system combines a peptide-based hydrogel with dynamic covalent bonding between boronic acid groups on the antibody and diol-based groups on the hydrogel scaffold. This reversible interaction slows the release of the antibody from the depot, extending therapeutic activity well beyond what is possible with conventional hydrogel delivery. The platform may also be combined with Fc-domain antibody modifications to extend circulation half-life, enabling further dose sparing.

Technical specifications

Core mechanism:

• Dynamic covalent bonding between boronic acid-functionalized antibodies and diol-functionalized peptide hydrogel
• Reversible interaction slows antibody diffusion out of the depot, enabling sustained release

Delivery format:

• Injectable liquid that spontaneously forms a hydrogel depot after injection
• Compatible with needle-based administration for outpatient or clinic use
• Designed for release durations exceeding six months, with potential for multi-year release

Therapeutic payload:

• Demonstrated with anti-TNF-alpha antibodies for inflammatory disease applications
• Applicable to other protein and biologic therapeutics
• Optional Fc-domain modification to extend circulation half-life and enable dose sparing

Optimization strategies under investigation:

• Switching antibody labeling from phenylboronic acid to benzoboroxole to shift the bonding equilibrium toward the bound state
• Increasing boronic acid labeling density on the antibody while preserving bioactivity
• Increasing the molar ratio of salicylhydroxamic acid groups on the peptide for more robust binding
• Replacing L-amino acid peptides with D-amino acid peptides to slow hydrogel clearance and remove the upper limit on release duration

Technology readiness level

The platform has been validated in a mouse study in which antibody release was sustained for more than two months, even though the study was not optimized for maximum duration. Several straightforward modifications, including increased labeling density, adjusted drug-to-hydrogel ratios, more stable dynamic covalent interactions, D-amino acid hydrogels, and Fc-modified antibodies, are expected to further extend release duration. Next steps include in vivo studies incorporating these optimizations, with the goal of achieving release durations of six months or longer and advancing toward translational development.