Urokinase-coated chitosan nanoparticles for thrombolytic therapy: preparation and pharmacodynamics in vivo

被引:35
作者
Jin, Hai-jiang [1 ]
Zhang, Hao [1 ]
Sun, Min-li [1 ]
Zhang, Bai-gen [1 ]
Zhang, Ji-wei [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Dept Vasc Surg, Ren Ji Hosp, Shanghai 200030, Peoples R China
关键词
Urokinase; Nanoparticles; Thrombolytic; Sustained-release; Water-soluble chitosan; ENCAPSULATED PLASMINOGEN ACTIVATORS; PLGA NANOPARTICLES; DELIVERY-SYSTEM; ACCELERATED THROMBOLYSIS; TARGETED THROMBOLYSIS; VITRO THROMBOLYSIS; DRUG-DELIVERY; NANOMEDICINE; ACID; STROKE;
D O I
10.1007/s11239-013-0951-7
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 +/- A 1.3 %, an encapsulation efficiency of 94.8 +/- A 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.
引用
收藏
页码:458 / 468
页数:11
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