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The Synthesis of RGD-functionalized Hydrogels as a Tool for Therapeutic Applications
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Cyclic RGD functionalized liposomes encapsulating urokinase for thrombolysis

Nengpan Zhang1, Chunlin Li2, Dayong Zhou3

  • 1School of Nano Technology and Nano Bionics, University of Science and Technology of China, Hefei 230026, China; CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.

Acta Biomaterialia
|February 8, 2018
PubMed

Insights

Targeted thrombolysis using cyclic RGD (cRGD) functionalized liposomes improved urokinase efficacy. These liposomes bind activated platelets, enhancing drug delivery and reducing dosage by 75% for effective thrombosis treatment.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Pharmacology

Background:

  • Thrombosis is a major cause of morbidity and mortality, often treated with thrombolytic drugs.
  • Current thrombolytic therapies have limitations including short plasma half-life and systemic side effects.
  • Urokinase is a widely used thrombolytic agent, but its clinical efficacy can be improved.

Purpose of the Study:

  • To develop and evaluate cyclic RGD (cRGD) functionalized liposomes for targeted delivery of urokinase.
  • To enhance thrombolytic efficacy and reduce systemic side effects of urokinase.
  • To investigate the binding specificity and drug release characteristics of cRGD-urokinase liposomes.

Main Methods:

  • Preparation of cRGD functionalized liposomes encapsulating urokinase.
  • Flow cytometry to assess binding of cRGD liposomes to activated platelets.
  • In vitro release studies to determine urokinase release kinetics.
  • In vitro and in vivo thrombolysis experiments using a mouse mesenteric thrombosis model.

Main Results:

  • cRGD liposomes specifically bind to activated platelets, not resting platelets.
  • Urokinase release from liposomes reached a plateau around 5 hours with 60% release.
  • In vitro experiments showed good thrombolysis potential for cRGD-urokinase liposomes.
  • In vivo studies demonstrated a 75% dose reduction of urokinase with equivalent thrombolytic effect compared to free urokinase.
  • cRGD liposomes improved thrombolytic efficacy by approximately 4-fold over free urokinase.

Conclusions:

  • cRGD functionalized liposomes offer a promising strategy for targeted thrombolysis.
  • Encapsulating urokinase in cRGD liposomes enhances its therapeutic efficacy and reduces required dosage.
  • This targeted drug delivery system holds significant potential for clinical application in treating thrombosis.

Keywords:
Platelet targetingThrombolysisThrombosis mouse modelUrokinasecRGD liposomes

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