Ordered and Kinetically Discrete Sequential Protein Release from Biodegradable Thin Films
Author(s)Jamieson, Kelsey S.; Hagerman, Samantha R.; Holler, Eggehard; Ljubimova, Julia Y.; Hammond, Paula T.; Hsu, Bryan Boen; ... Show more Show less
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Multidrug regimens can sometimes treat recalcitrant diseases when single-drug therapies fail. Recapitulating complex multidrug administration from controlled release films for localized delivery remains challenging because their release kinetics are frequently intertwined, and an initial burst release of each drug is usually uncontrollable. Kinetic control over protein release is demonstrated by cross-linking layer-by-layer films during the assembly process. We used biodegradable and naturally derived components and relied on copper-free click chemistry for bioorthogonal covalent cross-links throughout the film that entrap but do not modify the embedded protein. We found that this strategy restricted the interdiffusion of protein while maintaining its activity. By depositing a barrier layer and a second protein-containing layer atop this construct, we generated well-defined sequential protein release with minimal overlap that follows their spatial distribution within the film.
DepartmentMassachusetts Institute of Technology. Institute for Soldier Nanotechnologies; David H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Chemical Engineering; Massachusetts Institute of Technology. Department of Chemistry
Angewandte Chemie International Edition
Hsu, Bryan B., Kelsey S. Jamieson, Samantha R. Hagerman, Eggehard Holler, Julia Y. Ljubimova, and Paula T. Hammond. “Ordered and Kinetically Discrete Sequential Protein Release from Biodegradable Thin Films.” Angewandte Chemie International Edition 53, no. 31 (July 28, 2014): 8093–98.
Author's final manuscript