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Cited by 103Ultrasound and Hyperthermia ApplicationsNanoparticle-Based Drug DeliveryAdvanced Drug Delivery Systems

The DOI matches its Crossref record; 80 of the 81 references it cites were found in a registry or an index.

An ultrasound-responsive nano delivery system of tissue-type plasminogen activator for thrombolytic therapy

Uesugi, Yoshiko, Kawata, Hiroyuki, Jo, Jun-ichiro, Saito, Yoshihiko, Tabata, Yasuhiko·2010·Journal of Controlled Release
DOI 10.1016/j.jconrel.2010.07.127
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Abstract

This study is undertaken to design a novel nano-sized delivery system of tissue-type plasminogen activator (t-PA) which has a suppressed thrombolytic activity of t-PA, but recovered the activity only when exposed to ultrasound. Various amounts of ethylenediamine were chemically introduced into gelatin (cationized gelatins) to complex with t-PA. To modify the surface of complexes with polyethylene glycol (PEG), PEG was chemically grafted to the anionic gelatin (PEG-gelatin). The simple mixing with the PEG-gelatin enabled the t-PA-cationized gelatin complex to form a nano-sized delivery complex with PEG chains on the surface. The t-PA activity of PEG-modified complexes was significantly suppressed to be 45% of original t-PA. However, when exposed to ultrasound in vitro, the t-PA activity was fully recovered. A cell culture experiment demonstrated no cytotoxicity of PEG-modified complexes. The body distribution study indicated that the half-life of t-PA in the blood circulation was prolonged about 3 times. In a rabbit thrombosis model, the intravenous administration of PEG-modified complexes followed by ultrasound irradiation resulted in complete recanalization, in remarked contrast to the complex administration alone. It is concluded that the PEG-modified complex is a promising t-PA delivery system to enhance the biological activity at the site necessary only by a local ultrasound irradiation.

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Crossref · 10.1016/j.jconrel.2010.07.127

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Research works printed but not linked: 2

  1. Law, 2007, Stabilisation and targeted delivery of a fibrinolytic enzyme (nattokinase) by shellac, Minerva Biotecnol., 19, 17
  2. Rapoport, 2002, Ultrasound activation miceller drug delivery, Drug Deliv. Syst. Sci., 2, 37

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Metadata

Authors
Uesugi, Y., Kawata, H., Jo, J.-I., Saito, Y., & Tabata, Y.
Affiliations
  • Kyoto University (JP)
  • Nara Medical University (JP)
Corresponding author
Tabata, Yasuhiko
ORCID
Venue
Journal of Controlled Release
Publisher
Elsevier BV
Published
2010-10
Volume
147
Issue
2
Pages
269-277
ISSN
0168-3659 (ISSN-L)
DOI
10.1016/j.jconrel.2010.07.127
OpenAlex
W1966250539
Cited by
103
References
81
Citations by year
2026: 3 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 9 · 2020: 8 · 2019: 12 · 2018: 2 · 2017: 8 · 2016: 6 · 2015: 7 · 2014: 9 · 2013: 8 · 2012: 6
FWCI
3.59
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Journal of Controlled Release (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion)
  • Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
Funders
National Institute of Biomedical Innovation
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Ultrasound and Hyperthermia Applications
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
Keywords
tissue plasminogen activator, thrombolysis, ultrasound-responsive drug delivery, ethylenediamine, polyethylene glycol, PEGylation, thrombosis recanalization, blood circulation half-life, cytotoxicity
MeSH terms
Animals, Cell Line, Cell Survival, Disease Models, Animal, Drug Carriers, Ethylenediamines, Fibrinolytic Agents, Fibroblasts, Gelatin, Tissue Plasminogen Activator, Polyethylene Glycols, Rabbits, Surface Properties, Thrombosis, Tissue Distribution, Ultrasonic Therapy, Mice, Nanoparticles

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