A Customizable Antibody Delivery Strategy Using Fc-Affinity Ligands

Affinity-controlled release provides a versatile approach for the delivery of proteins from hydrogel systems by harnessing noncovalent interactions between a molecule of interest and a binding ligand. We present a strategy for the controlled release of native antibodies by leveraging affinity interactions with peptide ligands specific to the fragment crystallizable (Fc) region. Two Fc-binding ligands (FcLs) were engineered using distinct spacers, yielding different degrees of equilibrium dissociation constants (K_D) for the Fc region of human IgG₁: 2.54 ± 0.03 × 10^–8 M (HWRGWV-GAKSKG; FcL1) and 3.01 ± 0.09 × 10^–7 M (HWRGWV-K(PEG); FcLPEG). These ligands were immobilized within a chemically cross-linked hyaluronan-oxime hydrogel, where controlled release of bioactive bevacizumab was observed with FcL1 but not with the lower-affinity FcLPEG. To further explore the versatility of this approach, FcL1 was incorporated into a physically cross-linked hyaluronan-methylcellulose hydrogel, demonstrating tunable release of multiple IgG₁ antibodies, including bevacizumab and adalimumab, each over a 7-day period. Together, this work demonstrates a broadly applicable strategy to tune antibody release.