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Substrate Mediated Enzyme Prodrug Therapy

In this report, we detail Substrate Mediated Enzyme Prodrug Therapy (SMEPT) as a novel approach in drug delivery which relies on enzyme-functionalized cell culture substrates to achieve a localized conversion of benign prodrug(s) into active therapeutics with subsequent delivery to adhering cells or...

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Detalles Bibliográficos
Autores principales: Fejerskov, Betina, Zelikin, Alexander N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496709/
https://www.ncbi.nlm.nih.gov/pubmed/23152927
http://dx.doi.org/10.1371/journal.pone.0049619
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author Fejerskov, Betina
Zelikin, Alexander N.
author_facet Fejerskov, Betina
Zelikin, Alexander N.
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description In this report, we detail Substrate Mediated Enzyme Prodrug Therapy (SMEPT) as a novel approach in drug delivery which relies on enzyme-functionalized cell culture substrates to achieve a localized conversion of benign prodrug(s) into active therapeutics with subsequent delivery to adhering cells or adjacent tissues. For proof-of-concept SMEPT, we use surface adhered micro-structured physical hydrogels based on poly(vinyl alcohol), β-glucuronidase enzyme and glucuronide prodrugs. We demonstrate enzymatic activity mediated by the assembled hydrogel samples and illustrate arms of control over rate of release of model fluorescent cargo. SMEPT was not impaired by adhering cells and afforded facile time - and dose – dependent uptake of the in situ generated fluorescent cargo by hepatic cells, HepG2. With the use of a glucuronide derivative of an anticancer drug, SN-38, SMEPT afforded a decrease in cell viability to a level similar to that achieved using parent drug. Finally, dose response was achieved using SMEPT and administration of judiciously chosen concentration of SN-38 glucuronide prodrug thus revealing external control over drug delivery using drug eluting surface. We believe that this highly adaptable concept will find use in diverse biomedical applications, specifically surface mediated drug delivery and tissue engineering.
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spelling pubmed-34967092012-11-14 Substrate Mediated Enzyme Prodrug Therapy Fejerskov, Betina Zelikin, Alexander N. PLoS One Research Article In this report, we detail Substrate Mediated Enzyme Prodrug Therapy (SMEPT) as a novel approach in drug delivery which relies on enzyme-functionalized cell culture substrates to achieve a localized conversion of benign prodrug(s) into active therapeutics with subsequent delivery to adhering cells or adjacent tissues. For proof-of-concept SMEPT, we use surface adhered micro-structured physical hydrogels based on poly(vinyl alcohol), β-glucuronidase enzyme and glucuronide prodrugs. We demonstrate enzymatic activity mediated by the assembled hydrogel samples and illustrate arms of control over rate of release of model fluorescent cargo. SMEPT was not impaired by adhering cells and afforded facile time - and dose – dependent uptake of the in situ generated fluorescent cargo by hepatic cells, HepG2. With the use of a glucuronide derivative of an anticancer drug, SN-38, SMEPT afforded a decrease in cell viability to a level similar to that achieved using parent drug. Finally, dose response was achieved using SMEPT and administration of judiciously chosen concentration of SN-38 glucuronide prodrug thus revealing external control over drug delivery using drug eluting surface. We believe that this highly adaptable concept will find use in diverse biomedical applications, specifically surface mediated drug delivery and tissue engineering. Public Library of Science 2012-11-13 /pmc/articles/PMC3496709/ /pubmed/23152927 http://dx.doi.org/10.1371/journal.pone.0049619 Text en © 2012 Fejerskov, Zelikin http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Fejerskov, Betina
Zelikin, Alexander N.
Substrate Mediated Enzyme Prodrug Therapy
title Substrate Mediated Enzyme Prodrug Therapy
title_full Substrate Mediated Enzyme Prodrug Therapy
title_fullStr Substrate Mediated Enzyme Prodrug Therapy
title_full_unstemmed Substrate Mediated Enzyme Prodrug Therapy
title_short Substrate Mediated Enzyme Prodrug Therapy
title_sort substrate mediated enzyme prodrug therapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496709/
https://www.ncbi.nlm.nih.gov/pubmed/23152927
http://dx.doi.org/10.1371/journal.pone.0049619
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