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Desarrollo de implantes subcutáneos de liberación controlada de Carvedilol para la reducción sostenida de la presión arterial en modelos experimentales de hipertensión arterial;
Development of Subcutaneous Implants of Controlled Release Formulations of Carvedilol for Sustained Blood Pressure Reduction in Experimental Models of Hypertension

Creators:Allo, Miguel, Boquete, Camila Melody, Morettón, Marcela Analía, Parola, Luciano, SANTANDER PLANTAMURA, Yanina, Bertera, Facundo Martín, Chiappetta, Diego Andrés, HÖCHT, Christian

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Descripción

Objetivo: El objetivo del presente estudio fue el desarrollo y la evaluación farmacocinética y farmacodinámica de la liberaciónin vivo de implantes subcutáneos de carvedilol capaces de aportar niveles tisulares estables en modelos experimentales dehipertensión arterial.La incorporación del polímero hidrofílico SoluPlus (SP) en los implantes PCL:SP 150:150 y 50:250 favorece un incrementode la liberación de carvedilol dado que aporta concentraciones plasmáticas en el rango de 100-200 ng/mL durante 2 semanas,lo que tiene como resultado una reducción sostenida de la presión arterial sistólica indirecta en animales SHR.Material y métodos: Se prepararon implantes subcutáneos de poli (epsilon-caprolactona) (PCL) con diferentes proporcionesdel polímero hidrofílico SoluPlus (300:0; 250:50; 150:150 y 50:250 mg) cargados con 100 mg de carvedilol. Se evaluó el perfilplasmático y el efecto sobre la presión arterial sistólica (PAS) luego del implante de cada formulación en el tejido subcutáneode ratas espontáneamente hipertensas (REH) macho.Resultados: Las formulaciones PCL:SP 50:250 y 150:150 aportaron niveles en el rango de 100-200 ng/mL. Las formulacionesPCL:SP 250:50 y 300:0 aportaron concentraciones inferiores de carvedilol comprendidas en el rango de los 0-100 ng/mL duranteel transcurso del tratamiento. Los animales espontáneamente hipertensos tratados con PCL:SP 50:250 y 150:150 experimentaronun descenso significativo de la presión arterial sistólica (PCL:SP 50:250: DPAS: –36,6 ± 2,0 mmHg; PCL:SP150:150:35,7 ± 2,2 mmHg; p &lt;0,05 vs. basal).Conclusiones: La incorporación del polímero hidrofílico SoluPlus en los implantes PCL:SP 150:150 y 50:250 favorece un incrementode la liberación de carvedilol, ya que aporta concentraciones plasmáticas del β-bloqueante que aseguran una reducciónsostenida de la PAS indirecta en animales espontáneamente hipertensos. 

Objective: The aim of this study was the development and pharmacokinetic/pharmacodynamic evaluation of the in vivo releaseof subcutaneous implants of carvedilol capable of providing stable tissue levels in experimental models of hypertension.Methods: The subcutaneous implants were prepared with poly (epsilon-caprolactone) (PCL) and different proportions of theSoluPlus (SP) hydrophilic polymer (300:0; 250:50; 150:150 and 50:250 mg) loaded with 100 mg carvedilol. The plasma profileand the effect on systolic blood pressure (SBP) after subcutaneous implantation of each formulation was evaluated in malespontaneously hypertensive rats (SHR).Results: The PCL:SP 50:250 and 150:150 formulations provided levels ranging from 100 to 200 ng/mL and the PCL:SP 250:50and 300:0 formulations provided lower concentrations of carvedilol ranging from 0 to 100 ng/mL during the treatment period.Spontaneously hypertensive animals treated with the PCL:SP 50:250 y 150:150 implants presented a significant decrease inSBP (PCL:SP 50:250: DPAS: –36.6 ± 2.0 mm Hg; PCL:SP150:150: -35.7 ± 2.2 mmHg; p &lt;0.05 vs. baseline values)Conclusions: The incorporation of the SoluPlus hydrophilic polymer in PC:SP 150:150 and 50:250 implants increases therelease of carvedilol, since it provides plasma concentrations ranging from 100 to 200 ng/ml, resulting in a sustained reductionof indirect SBP in SHR.

Metadatos destacados

Colecciones
Argentine Journal of Cardiology

Editor

Sociedad Argentina de Cardiología

Fuente

Revista Argentina de Cardiología; Vol 88, No 2 (2020); 126-32, Argentine Journal of Cardiology; Vol 88, No 2 (2020); 126-32

Citación

Allo, Miguel et al., “Desarrollo de implantes subcutáneos de liberación controlada de Carvedilol para la reducción sostenida de la presión arterial en modelos experimentales de hipertensión arterial,” Archivo PPCT, consulta 2 de abril de 2026, http://archivoppct.caicyt.gov.ar/items/show/9686.

Dublin Core

Autor

Allo, Miguel
Boquete, Camila Melody
Morettón, Marcela Analía
Parola, Luciano
SANTANDER PLANTAMURA, Yanina
Bertera, Facundo Martín
Chiappetta, Diego Andrés
HÖCHT, Christian

Fuente

Revista Argentina de Cardiología; Vol 88, No 2 (2020); 126-32
Argentine Journal of Cardiology; Vol 88, No 2 (2020); 126-32

Editor

Sociedad Argentina de Cardiología

Fecha

2020-05-29

Derechos

Los que firman al pié, certificamos que tenemos total responsabilidad por la conducción de este estudio y por el diseño y la interpretación de los datos. Nosotros escribimos el manuscrito y somos responsables por la decisión acerca del mismo. Cada uno de nosotros cumple la definición de autor como se afirma en el Comité Internacional de Editores de Revistas Médicas (International Committee of Medical Journal Editors, ver www.icmje.org). Nosotros hemos visto y aprobado el manuscrito final. Ni el artículo, ni ninguna parte esencial del mismo, incluido las tablas y las figuras, será publicado o admitido para arbitrar a otra parte antes de aparecer en la Revista.También notificamos haber leído la sección “conflicto de intereses”, y revelaríamos cualquiera que existiera. Dejamos constancia que si nuestro artículo se publicara en la RAC, cederíamos los derechos (copyright) a la Revista.Los documentos publicados en esta revista están bajo la licencia Creative Commons Atribución-NoComercial-Compartir-Igual 2.5 Argentina.
Those signing below certify that we have full responsibility for the conduction of this study and for the design and interpretation of the information. We wrote the manuscript and are responsible for its decision. Each of us fulfills the definition of authorship as stated by the International Committee of Medical Journal Editors ( www.icmje.org). We have signed and approved the final manuscript. Neither the manuscript, nor any essential part thereof, including tables and figures, will be published or accepted for refereeing elsewhere before being published in the Journal. We have also read the "Conflict of Interest" section and would disclose any existing. We state that if our manuscript is published in the RAC, we shall transfer the copyright to the Journal.

Idioma

spa
eng

Tipo

info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion