title: Urokinase-coated chitosan nanoparticles for thrombolytic therapy: preparation and pharmacodynamics in vivo.
abstract: Blood reperfusion of affected limbs is the most effective therapy for peripheral vascular thrombotic disease, restoring nutrition and blood flow to threatened tissues. Because it is more cost-effective than other thrombolytics, urokinase (UK) is widely used to treat venous thrombosis in China. However, its use is limited because of the risk of UK-related hemorrhagic complications. UK-coated nanoparticles (NPs) may decrease adverse effects while simultaneously increasing thrombolytic benefits. The aim of this study was to combine the sustained-release properties of NPs with the clinical benefits of catheter-directed thrombolysis (CDT) to create a promising new therapy. NPs were prepared via self-assembled chitosan and tripolyphosphate, introduced into a thrombosis model in New Zealand white rabbits, and the ratio of the residual thrombus cross-sectional area to the vascular cross-sectional area was calculated. The NPs had a drug-bearing efficiency of 14.5 ± 1.3%, an encapsulation efficiency of 94.8 ± 2.1% while the particle size of UK-coated NPs was 236 nm. Transmission electron microscopy results showed that the shape of the NPs were spherical and regular. Whether delivered by intravenation or catheter, UK-coated NPs produced a significant increase in the thrombolytic effect compared with free UK and confirmed the superiority of CDT for improving clot lysis over drug-induced systemic thrombolysis. The intravenous NPs caused an abnormal increase in fibrinogen. In conclusion, a water-soluble UK-WCS-NP suspension with good encapsulation efficiency was easily prepared UK-WCS-NPs were capable of maintaining UK activity, provided sustained-release of UK and exhibited better thrombolytic function than free UK.
authors.affiliation: Department of Vascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, No. 145 Shandong Middle Road, Shanghai, China.
authors.forename: Hai-jiang
authors.initials: HJ
authors.lastname: Jin
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Min-li
authors.initials: ML
authors.lastname: Sun
authors.forename: Bai-gen
authors.initials: BG
authors.lastname: Zhang
authors.forename: Ji-wei
authors.initials: JW
authors.lastname: Zhang
mesh_terms: D000818:Animals; D048271:Chitosan / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D011817:Rabbits; D015912:Thrombolytic Therapy / Q000379:methods*; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D020246:Venous Thrombosis / Q000097:blood / Q000188:drug therapy
chemical_list: D048271:Chitosan; D014568:Urokinase-Type Plasminogen Activator