期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 20, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.nano.2019.03.014
关键词
Liposomes; Magnetic nanoparticles; Drug delivery; Recombinant tissue-type plasminogen activator; Thrombolysis
资金
- Ministry of Science and Technology, ROC [NSC 98-2120-M-182-001, NSC102-2221-E182-046]
- Chang Gung Memorial Hospital [CMRPD1E0013, BMRP432, BMRP249]
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@APA 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 degrees C vs. 37 degrees C was 53 +/- 11% vs. 81 +/- 3% in thromboelastograms, suggesting thermosensitive thrombolysis of TML@rtPA. In a rat embolic model with superfusion of 43 degrees 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. (C) 2019 Elsevier Inc. All rights reserved.
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