New approach to treating spinal cord injury using PEG-TAT-modified, cyclosporine-A-loaded PLGA/polymeric liposomes
New approach to treating spinal cord injury using PEG-TAT-modified, cyclosporine-A-loaded PLGA/polymeric liposomes
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DOI：
10.1080/1061186x.2016.1191082
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发表时间：
2017-01-01
影响因子：
4.5
通讯作者：
Feng, Shi-Qing
中科院分区：
文献类型：
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作者：
Gao, Shi-Jie;Liu, Yang;Feng, Shi-Qing
环孢霉素A（CsA）是一种免疫抑制剂，已显示出作为神经保护药物的有效性;然而，它不容易穿过血-脊髓屏障（BSCB），这限制了CsA用于治疗脊髓损伤（SCI）的临床应用。我们的小组最近测试了新型聚乙二醇（PEG）反式激活转导蛋白（达特）修饰的CsA负载的阳离子多功能聚合物脂质体-聚（乳酸-乙醇酸共聚物）（PLGA）核/壳纳米颗粒（PLGA/CsA NPs）转运和递送CsA穿过BSCB治疗SCI的能力。成功构建了PLGA/CsA纳米粒。体外药物释放研究表明，CsA从PLGA/CsA NPs中的持续释放发生在约25小时内。在这里提出的体内研究表明，受伤的动物，通过尾静脉接受PLGA/CsA纳米粒子，表现出显着的生长相关蛋白-43（GAP-43）的表达上调和GAP-43染色的神经元的数量增加相比，动物接受CsA或车辆单独。还通过Basso-Beattie-Bresnahan（BBB）旷场试验评价了神经功能的改善。此外，荧光素异硫氰酸酯（FITC）连接的PLGA/CsA纳米粒成功地聚集在完整的脊髓注射后4小时。我们的数据表明，PLGA/CsA纳米粒有可能作为一种新的治疗方法用于SCI。
Cyclosporine-A (CsA) is an immunosuppressant agent that has shown effectiveness as a neuroprotective drug; however, it does not readily cross the blood-spinal cord barrier (BSCB), which constrains the clinical applications of CsA for the treatment of spinal cord injury (SCI). Our group recently tested the ability of novel polyethylene glycol (PEG)-transactivating-transduction protein (TAT)-modified CsA-loaded cationic multifunctional polymeric liposome-poly(lactic-co-glycolic acid) (PLGA) core/shell nanoparticles (PLGA/CsA NPs) to transport and deliver CsA across the BSCB to treat SCI. The PLGA/CsA NPs were successfully constructed. In vitro drug release studies have demonstrated that the sustained release of CsA from PLGA/CsA NPs occurs over approximate to 25h. The in vivo study presented here showed that injured animals that received PLGA/CsA NPs through the tail vein, exhibited a significant up-regulation of growth-associated protein-43 (GAP-43) expression and an increased number of GAP-43-stained neurons compared with animals that received CsA or the vehicle alone. The improvement in neurological function was also evaluated by the Basso-Beattie-Bresnahan (BBB) open-field test. Moreover, fluorescein isothiocyanate (FITC)-attached PLGA/CsA NPs were successfully aggregated in the intact spinal cord 4h after injection. Our data suggest that PLGA/CsA NPs have the potential for use as a new treatment method for SCI.