Ordered and Kinetically Discrete Sequential Protein Release from Biodegradable Thin Films

摘要

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. Herein we demonstrate kinetic control over protein release by crosslinking 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 crosslinks 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.