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dc.contributor.author
Luján, Emmanuel
dc.contributor.author
Marino, Matias Daniel
dc.contributor.author
Olaiz, Nahuel Manuel
dc.contributor.author
Marshall, Guillermo Ricardo
dc.date.available
2021-11-30T19:50:50Z
dc.date.issued
2019-10-01
dc.identifier.citation
Luján, Emmanuel; Marino, Matias Daniel; Olaiz, Nahuel Manuel; Marshall, Guillermo Ricardo; Towards an optimal dose-response relationship in gene electrotransfer protocols; Pergamon-Elsevier Science Ltd; Electrochimica Acta; 319; 01-10-2019; 1002-1011
dc.identifier.issn
0013-4686
dc.identifier.uri
http://hdl.handle.net/11336/147786
dc.description.abstract
In search of an optimal gene electrotransfer (GET) protocol, an electroporation-based (EP) tumor treatment with great potential as a non-viral gene-delivery system, the concept of the dose-response relationship is introduced. It is shown that a reliable dose parameter is the pulse dosage and reliable response parameters are the reversibly electroporated tissue area as well as the unwanted damaged tissue area and plasmid damage due to pH. The standard stationary EP model consists in computing the reversibly electroporated tissue area in the first pulse as the region of tissue subjected to an electric field distribution higher than an electric field threshold for EP, where the electric field threshold comes from an experimental measurement and the electric field distribution from the solution of the nonlinear stationary Laplace equation for the electrostatic potential. The extended standard EP model introduced here consists in replicating for n consecutive pulses the standard EP model, via the experimental measurement in time of the successive thresholds. Because experimental data of this threshold variation is lacking, an exponential time decay function is assumed based on experimental measurements. The damage induced by pH fronts is defined as the tissue area subjected to pH abrupt changes above a basic threshold or below an acid threshold, where these changes come from numerical solutions via the electrolytic ablation (EA) model for EP-based protocols and the basic and acid thresholds from experiments. An optimal dose-response relationship in a GET protocol, for the range of pulse intensities with fixed pulse length and frequency, tested here, is predicted as the critical pulse dosage yielding maximum reversibly electroporated tissue area with minimal tissue area damage induced by pH fronts. Moreover, since damage induced by pH changes is proportional to the Coulomb dosage, damage induced by pH fronts is negligible in typical EP-based tumor protocols such as in electrochemotherapy (ECT) and irreversible electroporation (IRE) but not in GET, due to the most often longer pulses applied/used, i.e. higher dosage applied.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Pergamon-Elsevier Science Ltd
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
DOSE-RESPONSE
dc.subject
ELECTROPORATED-BASED TREATMENTS
dc.subject
GENE ELECTROTRANSFER
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IN SILICO MODELS
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Otras Ciencias de la Computación e Información
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Ciencias de la Computación e Información
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CIENCIAS NATURALES Y EXACTAS
dc.title
Towards an optimal dose-response relationship in gene electrotransfer protocols
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-11-25T16:11:52Z
dc.journal.volume
319
dc.journal.pagination
1002-1011
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Luján, Emmanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Simulación Computacional para Aplicaciones Tecnológicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina
dc.description.fil
Fil: Marino, Matias Daniel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; Argentina
dc.description.fil
Fil: Olaiz, Nahuel Manuel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; Argentina
dc.description.fil
Fil: Marshall, Guillermo Ricardo. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Computación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física del Plasma. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física del Plasma; Argentina
dc.journal.title
Electrochimica Acta
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0013468619313544?utm_campaign=STMJ_75273_AUTH_SERV_PPUB&utm_medium=email&utm_dgroup=Email1Publishing&utm_acid=-802396815&SIS_ID=-1&dgcid=STMJ_75273_AUTH_SERV_PPUB&CMX_ID=&utm_in=DM560956&utm_source=AC_30
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.electacta.2019.07.029
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