Displacement Affinity Release of Antibodies from Injectable Hydrogels

ACS Applied Materials & Interfaces
Vincent Huynh, Ryan Gavin Wylie

Abstract

Current methods to tune release rates of therapeutic antibodies (Abs) for local delivery are complex and routinely require bioconjugations that may reduce Ab bioactivity. To rapidly tune release profiles of bioactive Abs, we developed a biophysical interaction system within a neutravidin modified poly(carboxybetaine) hydrogel (pCB-NT) that tunes release rates of desthiobiotinylated Abs (D-Abs) using a constant hydrogel and D-Ab combination. Herein, we delivered desthiobiotinylated bevacizumab (D-Bv), a recombinant humanized monoclonal IgG1 Ab for antiangiogenic cancer therapies. D-Bv's high affinity for pCB-NT (KD 7.8 × 10-10 M; t1/2 ∼ 2 h) produces a slow D-Bv release rate (∼5 ng day-1) that is increased by the dissolution of hydrogel encapsulated biotin derivative pellets, which displaces D-Bv from pCB-NT binding sites. In contrast to traditional affinity systems, displacement affinity release of Abs (DARA) does not require Ab or hydrogel modifications for each unique release rate. D-Bv release rates were tuned by simply altering the total biotin derivative concentration; the effective first-order (keff) and mass per day release rates were tuned 25- and 8-fold, respectively. Local surface plasmon resonance (LSPR) and biolayer...Continue Reading

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Citations

Sep 18, 2020·Tissue Engineering. Part a·Shalini V GohilLakshmi S Nair
Sep 11, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Vittoria ChimissoCornelia G Palivan
May 4, 2021·Chemical Reviews·Santiago CorreaEric A Appel
Nov 26, 2019·ACS Applied Materials & Interfaces·Kongchang WeiClaudio Toncelli

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