Thrombolysis induced by intravenous administration of plasminogen activator in magnetoliposomes: dual targeting by magnetic and thermal manipulation.
Nanomedicine
; 20: 101992, 2019 08.
Article
en En
| MEDLINE
| ID: mdl-30981818
ABSTRACT
In previously published studies, intra-arterial (i.a.), but not intravenous (i.v.) delivery of recombinant tissue-type plasminogen activator (rtPA) immobilized on the surface of magnetic nanoparticles induces thrombolysis by magnetic targeting. We asked whether i.v. delivery of protected rtPA in a thermosensitive magnetoliposome (TML@rtPA) may achieve target thrombolysis. PEGylated TML@rtPA was optimized and characterized; controlled release of rtPA was achieved by thermodynamic and magnetic manipulation in vitro. The lysis index of TML@rtPA incubated with blood at 43 °C vs. 37 °C was 53⯱â¯11% vs. 81⯱â¯3% in thromboelastograms, suggesting thermosensitive thrombolysis of TML@rtPA. In a rat embolic model with superfusion of 43 °C saline on a focal spot on the iliac artery with clot lodging, release of rtPA equivalent to 20% regular dose from TML@rtPA administered i.a. vs. i.v. significantly restored iliac blood flow 15 vs. 55 min after clot lodging, respectively. TML@rtPA with magnetic guiding and focal hyperthermia may be potentially amendable to target thrombolysis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Terapia Trombolítica
/
Activador de Tejido Plasminógeno
/
Fenómenos Magnéticos
/
Hipertermia Inducida
Límite:
Animals
Idioma:
En
Revista:
Nanomedicine
Asunto de la revista:
BIOTECNOLOGIA
Año:
2019
Tipo del documento:
Article