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Biocatalytic polymer coatings: on-demand drug synthesis and localized therapeutic effect under dynamic cell culture conditions

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Biocatalytic polymer coatings : on-demand drug synthesis and localized therapeutic effect under dynamic cell culture conditions. / Fejerskov, Betina; Jensen, Najah B S; Mian Teo, Boon; Stadler, Brigitte Maria; Zelikin, Alexander N.

In: Small, Vol. 10, No. 7, 09.04.2014, p. 1314-24.

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@article{6e42a9ea61ba4cfda5b72da68799ab83,
title = "Biocatalytic polymer coatings: on-demand drug synthesis and localized therapeutic effect under dynamic cell culture conditions",
abstract = "Biocatalytic surface coatings are prepared herein for localized synthesis of drugs and their on-demand, site-specific delivery to adhering cells. This novel approach is based on the incorporation of an enzyme into multilayered polymer coatings to accomplish enzyme-prodrug therapy (EPT). The build-up of enzyme-containing multilayered coatings is characterized and correlations are drawn between the multilayer film assembly conditions and the enzymatic activity of the resulting coatings. Therapeutic effect elicited by the substrate mediated EPT (SMEPT) strategy is investigated using a prodrug for an anticancer agent, SN-38. The performance of biocatalytic coatings under flow conditions is investigated and it is demonstrated that EPT allows synthesizing the drugs on-demand, at the time desired and in a controllable amount to suit particular applications. Finally, using cells cultured in sequentially connected flow chambers, it is demonstrated that SMEPT affords a site-specific drug delivery, that is, exerts a higher therapeutic effect in cells adhering directly to the biocatalytic coatings than in the cells cultured {"}downstream{"}. Taken together, these data illustrate biomedical opportunities made possible by engineering tools of EPT into multilayered polymer coatings and present a novel, highly versatile tool for surface mediated drug delivery.",
author = "Betina Fejerskov and Jensen, {Najah B S} and {Mian Teo}, Boon and Stadler, {Brigitte Maria} and Zelikin, {Alexander N.}",
note = "{\textcopyright} 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
year = "2014",
month = apr,
day = "9",
doi = "10.1002/smll.201303101",
language = "English",
volume = "10",
pages = "1314--24",
journal = "Small",
issn = "1613-6810",
publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",
number = "7",

}

RIS

TY - JOUR

T1 - Biocatalytic polymer coatings

T2 - on-demand drug synthesis and localized therapeutic effect under dynamic cell culture conditions

AU - Fejerskov, Betina

AU - Jensen, Najah B S

AU - Mian Teo, Boon

AU - Stadler, Brigitte Maria

AU - Zelikin, Alexander N.

N1 - © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2014/4/9

Y1 - 2014/4/9

N2 - Biocatalytic surface coatings are prepared herein for localized synthesis of drugs and their on-demand, site-specific delivery to adhering cells. This novel approach is based on the incorporation of an enzyme into multilayered polymer coatings to accomplish enzyme-prodrug therapy (EPT). The build-up of enzyme-containing multilayered coatings is characterized and correlations are drawn between the multilayer film assembly conditions and the enzymatic activity of the resulting coatings. Therapeutic effect elicited by the substrate mediated EPT (SMEPT) strategy is investigated using a prodrug for an anticancer agent, SN-38. The performance of biocatalytic coatings under flow conditions is investigated and it is demonstrated that EPT allows synthesizing the drugs on-demand, at the time desired and in a controllable amount to suit particular applications. Finally, using cells cultured in sequentially connected flow chambers, it is demonstrated that SMEPT affords a site-specific drug delivery, that is, exerts a higher therapeutic effect in cells adhering directly to the biocatalytic coatings than in the cells cultured "downstream". Taken together, these data illustrate biomedical opportunities made possible by engineering tools of EPT into multilayered polymer coatings and present a novel, highly versatile tool for surface mediated drug delivery.

AB - Biocatalytic surface coatings are prepared herein for localized synthesis of drugs and their on-demand, site-specific delivery to adhering cells. This novel approach is based on the incorporation of an enzyme into multilayered polymer coatings to accomplish enzyme-prodrug therapy (EPT). The build-up of enzyme-containing multilayered coatings is characterized and correlations are drawn between the multilayer film assembly conditions and the enzymatic activity of the resulting coatings. Therapeutic effect elicited by the substrate mediated EPT (SMEPT) strategy is investigated using a prodrug for an anticancer agent, SN-38. The performance of biocatalytic coatings under flow conditions is investigated and it is demonstrated that EPT allows synthesizing the drugs on-demand, at the time desired and in a controllable amount to suit particular applications. Finally, using cells cultured in sequentially connected flow chambers, it is demonstrated that SMEPT affords a site-specific drug delivery, that is, exerts a higher therapeutic effect in cells adhering directly to the biocatalytic coatings than in the cells cultured "downstream". Taken together, these data illustrate biomedical opportunities made possible by engineering tools of EPT into multilayered polymer coatings and present a novel, highly versatile tool for surface mediated drug delivery.

U2 - 10.1002/smll.201303101

DO - 10.1002/smll.201303101

M3 - Journal article

C2 - 24376172

VL - 10

SP - 1314

EP - 1324

JO - Small

JF - Small

SN - 1613-6810

IS - 7

ER -