Triphenylphosphonium and D-α-tocopheryl polyethylene glycol 1000 succinate-modified, tanshinone IIA-loaded lipid-polymeric nanocarriers for the targeted therapy of myocardial infarction

被引：37
作者：
Zhang, Shouwen [1 ]
Li, Jingfang [1 ]
Hu, Shunpeng [1 ]
Wu, Fangfang [1 ]
Zhang, Xianzhao [1 ]
机构：
[1] Linyi Peoples Hosp, Dept Cardiol, 27 Jiefangludongduan, Linyi 276003, Shandong, Peoples R China
来源：
INTERNATIONAL JOURNAL OF NANOMEDICINE | 2018年 / 13卷
关键词：
myocardial infarction; mitochondria targeting; lipid-polymeric nanocarriers; D-alpha-tocopheryl polyethylene glycol 1000 succinate; triphenylphosphonium; tanshinone IIA; DRUG-DELIVERY; MIXED MICELLES; IN-VITRO; NANOPARTICLES; MITOCHONDRIA; ISCHEMIA; SYSTEM; CELLS; PHARMACOKINETICS; NANOMEDICINE;
D O I：
10.2147/IJN.S165590
中图分类号：
TB3 [工程材料学];
学科分类号：
0805 ; 080502 ;
摘要：
Background: Cardiovascular diseases (CVDs) are the leading causes of mortality worldwide. Currently, the best treatment options for myocardial infarction focus on the restoration of blood flow as soon as possible, which include reperfusion therapy, percutaneous coronary intervention, and therapeutic thrombolytic drugs. Materials and methods: In the present study, we report the development of lipid-polymeric nanocarriers (LPNs) for mitochondria-targeted delivery of tanshinone IIA (TN). D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was linked to the triphenylphosphonium (TPP) cation. The LPNs were fabricated by nanoprecipitation method. LPNs were evaluated in vitro and in vivo in comparison with free drugs and other similar nanocarriers. Results: The mean diameter of TN/nanoparticles (NPs) was 89.6 nm, while that of TN/LPNs was 121.3 nm. The zeta potential of TN/NPs and TN/LPNs was -33.6 and -22.3 mV, respectively. Compared with free TN and TN/NPs, TN/LPNs exhibited significantly improved compatibility and therapeutic efficiency. In addition, the in vivo pharmacokinetics, biodistribution, and infarct therapy studies in Sprague Dawley rats showed that TPP-TPGS/TN/LPNs had better efficiency than their nonmodified TN/LPNs counterparts in all respects. Conclusion: These results indicated that the TPP-TPGS/TN/LPNs were promising nanocarriers for efficient delivery of cardiovascular drugs and other therapeutic agents for the treatment of CVDs.
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页码：4045 / 4057
页数：13
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