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Human Neutrophil Elastase Responsive Delivery from Poly(ethylene glycol) Hydrogels

[Image: see text] A novel enzyme-responsive hydrogel drug delivery system was developed with the potential to treat inflammation locally. Human neutrophil elastase (HNE) is a serine protease secreted by neutrophils which are the first cells recruited to inflammatory sites. We exploited this cell-sec...

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Detalles Bibliográficos
Autores principales: Aimetti, Alex A., Tibbitt, Mark W., Anseth, Kristi S.
Formato: Texto
Lenguaje:English
Publicado: American Chemical Society 2009
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699883/
https://www.ncbi.nlm.nih.gov/pubmed/19408953
http://dx.doi.org/10.1021/bm9000926
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author Aimetti, Alex A.
Tibbitt, Mark W.
Anseth, Kristi S.
author_facet Aimetti, Alex A.
Tibbitt, Mark W.
Anseth, Kristi S.
author_sort Aimetti, Alex A.
collection PubMed
description [Image: see text] A novel enzyme-responsive hydrogel drug delivery system was developed with the potential to treat inflammation locally. Human neutrophil elastase (HNE) is a serine protease secreted by neutrophils which are the first cells recruited to inflammatory sites. We exploited this cell-secreted enzyme as a biological cue for controlled release. HNE sensitive peptide linkers were immobilized within poly(ethylene glycol) hydrogels using photopolymerization techniques. The kinetics of the enzyme reaction within the gel was tailored by varying the amino acid residues present in the P1 and P1′ substrate positions (immediately adjacent to cleavage location). A novel FRET-based hydrogel platform was designed to characterize the accessibility of the substrate within the cross-linked, macroscopic hydrogel. Lastly, a diffusion-reaction mathematical model with Michaelis−Menten kinetics was developed to predict the overall release profile and captured the initial 80% of the experimentally observed release. The hydrogel platform presented shows highly controlled release kinetics with potential applications in cellular responsive drug delivery.
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spelling pubmed-26998832009-06-22 Human Neutrophil Elastase Responsive Delivery from Poly(ethylene glycol) Hydrogels Aimetti, Alex A. Tibbitt, Mark W. Anseth, Kristi S. Biomacromolecules [Image: see text] A novel enzyme-responsive hydrogel drug delivery system was developed with the potential to treat inflammation locally. Human neutrophil elastase (HNE) is a serine protease secreted by neutrophils which are the first cells recruited to inflammatory sites. We exploited this cell-secreted enzyme as a biological cue for controlled release. HNE sensitive peptide linkers were immobilized within poly(ethylene glycol) hydrogels using photopolymerization techniques. The kinetics of the enzyme reaction within the gel was tailored by varying the amino acid residues present in the P1 and P1′ substrate positions (immediately adjacent to cleavage location). A novel FRET-based hydrogel platform was designed to characterize the accessibility of the substrate within the cross-linked, macroscopic hydrogel. Lastly, a diffusion-reaction mathematical model with Michaelis−Menten kinetics was developed to predict the overall release profile and captured the initial 80% of the experimentally observed release. The hydrogel platform presented shows highly controlled release kinetics with potential applications in cellular responsive drug delivery. American Chemical Society 2009-05-01 2009-06-08 /pmc/articles/PMC2699883/ /pubmed/19408953 http://dx.doi.org/10.1021/bm9000926 Text en Copyright © 2009 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org. 40.75
spellingShingle Aimetti, Alex A.
Tibbitt, Mark W.
Anseth, Kristi S.
Human Neutrophil Elastase Responsive Delivery from Poly(ethylene glycol) Hydrogels
title Human Neutrophil Elastase Responsive Delivery from Poly(ethylene glycol) Hydrogels
title_full Human Neutrophil Elastase Responsive Delivery from Poly(ethylene glycol) Hydrogels
title_fullStr Human Neutrophil Elastase Responsive Delivery from Poly(ethylene glycol) Hydrogels
title_full_unstemmed Human Neutrophil Elastase Responsive Delivery from Poly(ethylene glycol) Hydrogels
title_short Human Neutrophil Elastase Responsive Delivery from Poly(ethylene glycol) Hydrogels
title_sort human neutrophil elastase responsive delivery from poly(ethylene glycol) hydrogels
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699883/
https://www.ncbi.nlm.nih.gov/pubmed/19408953
http://dx.doi.org/10.1021/bm9000926
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