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Injectable Supramolecular Polymer-Nanoparticle Hydrogels for Cell and Drug Delivery Applications

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Injectable Granular Hydrogels Enable Avidity-Controlled Biotherapeutic Delivery.

Arielle M D'Elia¹, Olivia L Jones¹, Gabriela Canziani²

¹School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, Pennsylvania 19104, United States.

ACS Biomaterials Science & Engineering

|February 15, 2024

Summary

This study introduces an affinity-based hydrogel system for sustained, localized protein delivery, overcoming limitations of conventional methods for treating diseases like cancer.

Keywords:

avidity bioconjugation cyclodextrin hydrogel sustained release

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Area of Science:

Biomaterials Science
Drug Delivery
Protein Therapeutics

Background:

Protein therapeutics offer promise for diseases like cancer but suffer from off-target effects and short half-lives with systemic delivery.
Localized and controlled delivery systems are needed to improve therapeutic efficacy and reduce side effects.

Purpose of the Study:

To develop an affinity-based protein delivery system utilizing guest-host complexation for sustained, localized biomolecule presentation.
To engineer shear-thinning and self-healing granular hydrogels for minimally invasive delivery of protein therapeutics.

Main Methods:

Hydrogels were synthesized via copolymerization of methacrylated β-cyclodextrin (host) and methacrylated dextran.
Guest-host complexation between adamantane-modified proteins and β-cyclodextrin hydrogels was utilized.
Bovine serum albumin (BSA) was conjugated to adamantane, and its binding affinity and complex half-life were characterized.

Main Results:

Granular hydrogels (32.4 ± 16.4 μm) exhibited shear-thinning and self-healing properties suitable for minimally invasive delivery.
Adamantane-BSA conjugates showed tunable avidity, leading to a fourfold increase in complex half-life and a fivefold reduction in protein release over 28 days.
Conjugation of adamantane to cytokines (IL-4, IL-10, IFNγ) preserved bioactivity and enabled sustained release.

Conclusions:

The developed affinity-based hydrogel system enables sustained local presentation of protein therapeutics.
Avidity-controlled delivery strategy is a promising approach for enhancing the efficacy of protein-based drugs in various biomedical applications.