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...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3496709?pdf=render |
| _version_ | 1828462249981771776 |
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| author | Betina Fejerskov Alexander N Zelikin |
| author_facet | Betina Fejerskov Alexander N Zelikin |
| author_sort | Betina Fejerskov |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-11T02:33:01Z |
| format | Article |
| id | doaj.art-0d588bb8467a41c2b7eb33c508487a36 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T02:33:01Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0d588bb8467a41c2b7eb33c508487a362022-12-22T01:23:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e4961910.1371/journal.pone.0049619Substrate mediated enzyme prodrug therapy.Betina FejerskovAlexander N ZelikinIn 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.http://europepmc.org/articles/PMC3496709?pdf=render |
| spellingShingle | Betina Fejerskov Alexander N Zelikin Substrate mediated enzyme prodrug therapy. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC3496709?pdf=render |
| work_keys_str_mv | AT betinafejerskov substratemediatedenzymeprodrugtherapy AT alexandernzelikin substratemediatedenzymeprodrugtherapy |