Displacement Affinity Release of Antibodies from Injectable Hydrogels

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Biophysics

Background:

• Current methods for tuning therapeutic antibody (Ab) release rates for local delivery are complex, often requiring bioconjugations that can reduce Ab bioactivity.
• There is a need for simpler, more efficient methods to control the release profiles of bioactive therapeutic antibodies.

Purpose of the Study:

• To develop a biophysical interaction system for rapidly tuning the release rates of bioactive antibodies from hydrogels.
• To demonstrate the efficacy of this system using desthiobiotinylated bevacizumab (D-Bv) for antiangiogenic cancer therapy.

Main Methods:

• A neutravidin-modified poly(carboxybetaine) hydrogel (pCB-NT) was developed to bind desthiobiotinylated antibodies (D-Abs).
• Release rates were tuned by displacing D-Abs from the hydrogel using biotin derivative pellets, a method termed displacement affinity release of Abs (DARA).
• Local surface plasmon resonance (LSPR) and biolayer interferometry (BLI) were used to confirm binding affinities.

Main Results:

• The DARA system successfully tuned D-Bv release rates over 25-fold (effective first-order) and 8-fold (mass per day).
• D-Bv exhibited high affinity for the pCB-NT hydrogel (K_D 7.8 × 10^-10 M), resulting in a slow baseline release rate.
• Altering biotin derivative concentration effectively controlled D-Bv release without modifying the antibody or hydrogel.

Conclusions:

• The DARA system provides a versatile and straightforward approach to tune therapeutic antibody release rates for local delivery.
• This biophysical interaction system is amenable to various anticancer antibodies for diverse therapeutic applications, including receptor blockade and immune cell recruitment.
• The DARA method avoids complex bioconjugations, preserving antibody bioactivity and simplifying the drug delivery process.