Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 57, Issue 13, Pages 3406-3410Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201713428
Keywords
antibodies; competitive interactions; drug delivery; materials science; protein modifications
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Funding
- Natural Sciences and Engineering Research Council (NSERC)
- Canada Foundation for Innovation: JohnR. Evans Leaders Fund (CFI-JELF)
- Ontario Research Fund Research Infrastructure (ORI-RI)
- McMaster University
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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 100days.
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