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Ordered and Kinetically Discrete Sequential Protein Release from Biodegradable Thin Films
Author(s) -
Hsu Bryan B.,
Jamieson Kelsey S.,
Hagerman Samantha R.,
Holler Eggehard,
Ljubimova Julia Y.,
Hammond Paula T.
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201403702
Subject(s) - bioorthogonal chemistry , kinetics , drug delivery , layer (electronics) , chemistry , controlled release , click chemistry , biophysics , nanotechnology , combinatorial chemistry , materials science , biology , physics , quantum mechanics
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.