A dendronized polymer variant that facilitates safe delivery of a calcium channel antagonist to the heart.
Nanomedicine
; 29: 102264, 2020 10.
Article
en En
| MEDLINE
| ID: mdl-32659322
ABSTRACT
Therapeutic approaches for myocardial ischemia-reperfusion injury (MI) have been ineffective due to limited bioavailability and poor specificity. We have previously shown that a peptide that targets the α-interaction domain of the cardiac L-type calcium channel (AID-peptide) attenuates MI when tethered to transactivator of transcription sequence (TAT) or spherical nanoparticles. However some reservations remain regarding use of these delivery platforms due to the relationship with human immunodeficiency virus, off-target effects and toxicity. Here we investigate the use of linear dendronized polymers (denpols) to deliver AID-peptide as a potential MI therapy using in vitro, ex vivo and in vivo models. Optimized denpol-complexed AID-peptide facilitated in vitro cardiac uptake of AID-peptide, and reduced MI. Maximal in vivo cardiac uptake was achieved within the 2â¯h therapeutic time window for acute myocardial infarction. Importantly, optimized denpol-complexed AID-peptide was not toxic. This platform may represent an alternative therapeutic approach for the prevention of MI.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Bloqueadores de los Canales de Calcio
/
Daño por Reperfusión Miocárdica
/
Canales de Calcio Tipo L
/
Nanopartículas
/
Corazón
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nanomedicine
Asunto de la revista:
BIOTECNOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Australia