Competitive Affinity Release for Long-Term Delivery of Antibodies from Hydrogels

Abstract

With increased clinical use of antibodies, long-term delivery strategies are needed to decrease injection frequency and improve health outcomes. A three-component drug-delivery system was developed for competitive affinity release of a streptavidin-antibody conjugate from agarose-desthiobiotin hydrogels via controlled dissolution of sparingly soluble biotin derivatives. The antibody conjugate was localized in the hydrogel through streptavidin-desthiobiotin complexation. Dissolution of sparingly soluble biotin derivatives disrupts streptavidin-desthiobiotin complexation for controlled release of the antibody conjugate. Release was tuned by altering the total biotin derivative concentration without further hydrogel or antibody modification. First-order tunable release of bioactive Avastin, a therapeutic anti-VEGF antibody, was demonstrated from a non-cytotoxic system for over 100 days.

Keywords: antibodies; competitive interactions; drug delivery; materials science; protein modifications.