Ordered and Kinetically Discrete Sequential Protein Release from Biodegradable Thin Films

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 relea...

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Main Authors: Jamieson, Kelsey S., Hagerman, Samantha R., Holler, Eggehard, Ljubimova, Julia Y., Hsu, Bryan Boen, Hammond, Paula T
Other Authors: Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies
Format: Article
Language:en_US
Published: Wiley Blackwell 2016
Online Access:http://hdl.handle.net/1721.1/101182
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author Jamieson, Kelsey S.
Hagerman, Samantha R.
Holler, Eggehard
Ljubimova, Julia Y.
Hsu, Bryan Boen
Hammond, Paula T
author2 Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies
author_facet Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies
Jamieson, Kelsey S.
Hagerman, Samantha R.
Holler, Eggehard
Ljubimova, Julia Y.
Hsu, Bryan Boen
Hammond, Paula T
author_sort Jamieson, Kelsey S.
collection MIT
description 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.
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spelling mit-1721.1/1011822022-09-30T20:37:59Z Ordered and Kinetically Discrete Sequential Protein Release from Biodegradable Thin Films Jamieson, Kelsey S. Hagerman, Samantha R. Holler, Eggehard Ljubimova, Julia Y. Hsu, Bryan Boen Hammond, Paula T Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Chemistry Koch Institute for Integrative Cancer Research at MIT Hsu, Bryan Boen Jamieson, Kelsey S. Hagerman, Samantha R. Hammond, Paula T. 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. United States. Army Research Office (Contract W911NF-13-D-0001) United States. Air Force (Contract W911NF-07-D-0004) 2016-02-16T13:17:16Z 2016-02-16T13:17:16Z 2014-06 2014-03 Article http://purl.org/eprint/type/JournalArticle 14337851 1521-3773 http://hdl.handle.net/1721.1/101182 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. en_US http://dx.doi.org/10.1002/anie.201403702 Angewandte Chemie International Edition Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Blackwell PMC
spellingShingle Jamieson, Kelsey S.
Hagerman, Samantha R.
Holler, Eggehard
Ljubimova, Julia Y.
Hsu, Bryan Boen
Hammond, Paula T
Ordered and Kinetically Discrete Sequential Protein Release from Biodegradable Thin Films
title Ordered and Kinetically Discrete Sequential Protein Release from Biodegradable Thin Films
title_full Ordered and Kinetically Discrete Sequential Protein Release from Biodegradable Thin Films
title_fullStr Ordered and Kinetically Discrete Sequential Protein Release from Biodegradable Thin Films
title_full_unstemmed Ordered and Kinetically Discrete Sequential Protein Release from Biodegradable Thin Films
title_short Ordered and Kinetically Discrete Sequential Protein Release from Biodegradable Thin Films
title_sort ordered and kinetically discrete sequential protein release from biodegradable thin films
url http://hdl.handle.net/1721.1/101182
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