Pharmaceutical Research

, Volume 30, Issue 6, pp 1663–1676 | Cite as

Thrombus-Targeted Nanocarrier Attenuates Bleeding Complications Associated with Conventional Thrombolytic Therapy

  • Shahriar Absar
  • Kamrun Nahar
  • Young Min Kwon
  • Fakhrul Ahsan
Research Paper



To test the hypothesis that thrombus-specific tissue plasminogen activator (tPA)-loaded nanocarriers enhance thrombolytic efficacy and attenuate hemorrhagic complications.


A series of pegylated and non-pegylated tPA-loaded liposomes were prepared and their surfaces were decorated with the peptide sequence (CQQHHLGGAKQAGDV) of fibrinogen gamma-chain that binds with GPIIb/IIIa expressed on activated platelets. All formulations were characterized for physical properties, stability and in vitro release profile. The thrombolytic activities of tPA-loaded liposomes were tested by visual end-point detection, fibrin agar-plate and human blood clot-lysis assays. The thrombus-specificity of the peptide-modified-liposomes was evaluated by studying the binding of fluorescent peptide-liposomes with activated platelets. The pharmacokinetic profile and thrombolytic efficacy were evaluated in healthy rats and an inferior vena-cava rat model of thrombosis, respectively.


Both pegylated and non-pegylated peptide-modified-liposomes showed favorable physical characteristics and colloidal stability. Formulations exhibited an initial burst release (40–50% in 30 min) followed by a continuous release of tPA (80–90% in 24 h) in vitro. Encapsulated tPA retained >90% fibrinolytic activity as compared to that of native tPA. Peptide-grafted-liposomes containing tPA demonstrated an affinity to bind with activated platelets. The half-life of tPA was extended from 7 to 103 and 141 min for non-pegylated and pegylated liposomes, respectively. Compared to native tPA, liposomal-tPA caused a 35% increase in clot-lysis, but produced a 4.3-fold less depletion of circulating fibrinogen.


tPA-loaded homing-peptide-grafted-liposomes demonstrate enhanced thrombolytic activity with reduced hemorrhagic risk.


localized fibrinolysis peptide-modified-liposomes protein delivery targeted delivery tissue plasminogen activator 



Acute myocardial infarction


Analysis of variance


Area under the curve


Bovine serum albumin




1,2-Dioleoyl-sn-Glycero-3-Phosphoethanolamine (DOPE)


1,2-distearoyl-sn-glycero-3-Phosphoethanolamine-N-[maleimide(polyethylene glycol)-2000]




Fluorescein isothiocyanate


Glycoprotein IIb/IIIa


Inferior vena cava


Plasminogen activator


Plasminogen activator inhibitor-1


Phosphate buffered saline




Percutaneous coronary intervention


Polydispersity index


Polyethylene glycol


Platelet rich plasma


Room temperature


Standard deviation


N-Succinimidyl1, 3-(2-pyridyldithio)propionate




Tissue plasminogen activator



The authors would like thank Dr. Imam Shaik and Kowser Miah for their technical assistance in developing the thrombosis model. We also thank Mr. George Littlejohn at the Coffee Memorial Blood Center (Amarillo, TX) for providing us with human plasma sample. The work was supported by the internal fund of TTUHSC.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Shahriar Absar
    • 1
  • Kamrun Nahar
    • 1
  • Young Min Kwon
    • 1
    • 2
  • Fakhrul Ahsan
    • 1
  1. 1.Department of Pharmaceutical SciencesTexas Tech University Health Sciences CenterAmarilloUSA
  2. 2.Department of Pharmaceutical Sciences, College of PharmacyNova Southeastern UniversityFort LauderdaleUSA

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