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Título
Elastin-like recombinamer-based devices releasing Kv1.3 blockers for the prevention of intimal hyperplasia: An in vitro and in vivo study
Autor
Año del Documento
2020
Editorial
Elsevier
Descripción
Producción Científica
Documento Fuente
Acta Biomaterialia, octubre 2020, vol. 115, p. 264-274.
Resumen
Coronary artery disease (CAD) is the most common cardiovascular disorder. Vascular surgery strategies for coronary revascularization (either percutaneous or open) show a high rate of failure because of restenosis of the vessel, due to phenotypic switch of vascular smooth muscle cells (VSMCs) leading to proliferation and migration. We have previously reported that the inhibition of Kv1.3 channel function with selective blockers represents an effective strategy for the prevention of restenosis in human vessels used for coronary angioplasty procedures. However, delivery systems for controlled release of these drugs have not been investigated. Here we tested the efficacy of several formulations of elastin like recombinamers (ELRs) hydrogels to deliver the Kv1.3 blocker PAP-1 in various restenosis models. The dose and time course of PAP-1 release from ELRs click hydrogels was able to inhibit human VSMC proliferation in vitro as well as remodeling of human vessels in organ culture and restenosis in in vivo models. We conclude that this combination of active compound and advanced delivery method could improve the outcomes of vascular surgery in patients. STATEMENT OF SIGNIFICANCE: Vascular surgery strategies for coronary revascularization show a high rate of failure, because of occlusion (restenosis) of the vessel, due to vascular smooth muscle cells proliferation and migration. We have previously reported that blockers of Kv1.3 channels represent an effective anti-restenosis therapy, but delivery systems for their controlled release have not being explored. Here we tested the efficacy of several formulations of elastin like recombinamers (ELRs) hydrogels to deliver the Kv1.3 blocker PAP-1 in various restenosis models, both in vivo and in vitro, and also in human vessels. We demonstrated that combination of active compound and advanced delivery method could improve the outcomes of vascular surgery in patients.
Materias Unesco
23 Química
32 Ciencias Médicas
Palabras Clave
Vascular smooth muscle cells
Intimal hyperplasia
Elastin-like recombinamers
Hydrogels
Kv1.3 channels
Local drug delivery
ISSN
1742-7061
Revisión por pares
SI
Patrocinador
Unión Europea-Horizonte 2020 (EU H2020-NMP-2014-646075)
Ministerio de Economía y Competitividad (BFU2016-75360-R, DTS19/00162, MAT2016-79435-R, MAT2016-78903-R, RTI2018-096320-B-C22)
Junta de Castilla y León (VA114P17, VA317P18)
Centro en Red de Medicina regenerativa y Terapia celular de Castilla y León
Ministerio de Economía y Competitividad (BFU2016-75360-R, DTS19/00162, MAT2016-79435-R, MAT2016-78903-R, RTI2018-096320-B-C22)
Junta de Castilla y León (VA114P17, VA317P18)
Centro en Red de Medicina regenerativa y Terapia celular de Castilla y León
Version del Editor
Propietario de los Derechos
© 2020 Acta Materialia Inc
Idioma
eng
Tipo de versión
info:eu-repo/semantics/acceptedVersion
Derechos
openAccess
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