Tuning hydrogel affinity to control the release of antibodies

Area of Science:

• Biomaterials Science
• Ophthalmology
• Drug Delivery

Background:

• Specific affinity interactions enable functional hydrogels for tunable protein release.
• Antibody-based therapeutics offer potential for treating eye conditions but require effective delivery systems.

Purpose of the Study:

• To explore controlled release of antibody therapeutics using affinity interactions with immobilized peptide ligands within a hydrogel.
• To develop a dual-antibody delivery strategy for stimulating retinal stem cells in the adult mammalian eye.

Main Methods:

• Functionalization of a hyaluronan-based hydrogel with a specific fragment crystallizable domain peptide ligand (FcL).
• Utilized oxime chemistry for hydrogel crosslinking and inverse electron demand Diels-Alder for FcL conjugation.
• Investigated in vitro protein retention and stability, and in vivo efficacy in adult CD1 mice via intravitreal injection.

Main Results:

• FcL-functionalized hydrogels demonstrated affinity-mediated retention of antibodies, reducing burst release and preserving protein stability.
• A single intravitreal injection of the hydrogel formulation effectively stimulated retinal stem cells over four days.
• Hydrogel delivery matched the efficacy of three repeated bolus injections, highlighting advantages over traditional administration.

Conclusions:

• The developed hydrogel platform enables controlled, sustained release of antibody therapeutics through non-covalent affinity interactions.
• This technology shows significant potential for various antibody-based therapies and offers a promising approach for local ocular drug delivery.