title: Ordered and kinetically discrete sequential protein release from biodegradable thin films.
abstract: 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.
authors.affiliation: Koch Institute for Integrative Cancer Research and the Institute for Soldier Nanotechnologies, Massachusetts Institute for Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 (USA); Department of Chemistry, Massachusetts Institute for Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 (USA).
authors.forename: Bryan B
authors.initials: BB
authors.lastname: Hsu
authors.forename: Kelsey S
authors.initials: KS
authors.lastname: Jamieson
authors.forename: Samantha R
authors.initials: SR
authors.lastname: Hagerman
authors.forename: Eggehard
authors.initials: E
authors.lastname: Holler
authors.forename: Julia Y
authors.initials: JY
authors.lastname: Ljubimova
authors.forename: Paula T
authors.initials: PT
authors.lastname: Hammond
mesh_terms: D007700:Kinetics; D011506:Proteins / Q000378:metabolism*
chemical_list: D011506:Proteins
keywords: click chemistry; controlled release; drug delivery; polyelectrolyte multilayers; staged release