Preparation of thermosensitive magnetic liposome encapsulated recombinant tissue plasminogen activator for targeted thrombolysis
Preparation of thermosensitive magnetic liposome encapsulated recombinant tissue plasminogen activator for targeted thrombolysis
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DOI：
10.1016/j.jmmm.2016.10.122
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发表时间：
2017-04-01
影响因子：
2.7
通讯作者：
Chen, Jyh-Ping
中科院分区：
文献类型：
--
作者：
Hsu, Hao-Lung;Chen, Jyh-Ping
以1，2-二棕榈酰-sn-甘油-3-磷酸胆碱、二硬脂酰磷脂酰乙醇胺-N-聚乙二醇2000、胆固醇和Fe 3 O 4磁性纳米粒为原料，采用溶剂挥发/超声法和冻融法制备温敏磁性脂质体（TML），包封重组组织型纤溶酶原激活剂（rtPA）。响应面法是预测药物包封率和温度敏感性释放的有效工具。验证实验验证了模型的准确性，该模型为制备具有可控包封率和可预测的温度敏感性药物释放行为的TML提供了简单有效的方法。采用动态光散射、透射电镜、X射线衍射和差示扫描量热法对样品进行了表征。rtPA的温度敏感性释放可以从体外溶栓实验中得到证实。使用TML的血栓溶解药物递送系统可以被提出用于将rtPA磁性靶向递送到血栓部位，然后在交变磁场中温度触发控制药物释放。
Recombinant tissue plasminogen activator (rtPA) was encapsulated in thermosensitive magnetic liposome (TML) prepared from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, distearolyphosphatidyl ethanolamine-Npoly(ethylene glycol) 2000, cholesterol and Fe3O4 magnetic nanoparticles by solvent evaporation/sonication and freeze-thaw cycles method. Response surface methodology was proved to be a powerful tool to predict the drug encapsulation efficiency and temperature-sensitive drug release. Validation experiments verified the accuracy of the model that provides a simple and effective method for fabricating TML with controllable encapsulation efficiency and predictable temperature-sensitive drug release behavior. The prepared samples were characterized for physico-chemical properties by dynamic light scattering, transmission electron microscopy, X-ray diffraction and differential scanning calorimetry. Temperature-sensitive release of rtPA could be confirmed from in vitro thrombolysis experiments. A thrombolytic drug delivery system using TML could be proposed for magnetic targeted delivery of rtPA to the site of thrombus followed by temperature-triggered controlled drug release in an alternating magnetic field.