Thrombolysis induced by intravenous administration of plasminogen activator in magnetoliposomes: dual targeting by magnetic and thermal manipulation

Chih-Hsin Liu; Hao-Lung Hsu; Jyh-Ping Chen; Tony Wu; Yunn-Hwa Ma

doi:10.1016/j.nano.2019.03.014

Thrombolysis induced by intravenous administration of plasminogen activator in magnetoliposomes: dual targeting by magnetic and thermal manipulation

Nanomedicine. 2019 Aug:20:101992. doi: 10.1016/j.nano.2019.03.014. Epub 2019 Apr 11.

Authors

Chih-Hsin Liu¹, Hao-Lung Hsu², Jyh-Ping Chen³, Tony Wu⁴, Yunn-Hwa Ma⁵

Affiliations

¹ Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan, ROC; Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC.
² Department of Chemical and Materials Engineering, College of Engineering, Chang Gung University, Taoyuan, Taiwan, ROC.
³ Department of Chemical and Materials Engineering, College of Engineering, Chang Gung University, Taoyuan, Taiwan, ROC; Department of Materials Engineering, Ming Chi University of Technology, New Taipei City, Taiwan, ROC; Department of Plastic and Reconstructive Surgery and Craniofacial Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; Research Center for Chinese Herbal Medicine and Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan, ROC.
⁴ Department of Neurology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
⁵ Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Department of Neurology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC. Electronic address: yhma@mail.cgu.edu.tw.

PMID: 30981818
DOI: 10.1016/j.nano.2019.03.014

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 ± 11% vs. 81 ± 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.

Keywords: Drug delivery; Liposomes; Magnetic nanoparticles; Recombinant tissue-type plasminogen activator; Thrombolysis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Intravenous
Animals
Biocompatible Materials / chemistry
Hyperthermia, Induced*
Liposomes
Magnetic Phenomena*
Male
Nanocomposites / chemistry
Nanocomposites / ultrastructure
Particle Size
Rats, Sprague-Dawley
Temperature
Thrombolytic Therapy*
Thrombosis
Tissue Plasminogen Activator / administration & dosage*

Substances

Biocompatible Materials
Liposomes
Tissue Plasminogen Activator