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采用三种互补方法对胎盘靶向给药的有效性和安全性进行综合评价

Comprehensive Evaluation of the Effectiveness and Safety of Placenta-Targeted Drug Delivery Using Three Complementary Methods.

作者信息

Zhang Baozhen, Chen Zhilong, Han Jinyu, Li Mengxia, Nayak Nihar R, Fan Xiujun

机构信息

Laboratory for Reproductive Health, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences.

Laboratory for Reproductive Health, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences; College of Veterinary Medicine, Hunan Agricultural University.

出版信息

J Vis Exp. 2018 Sep 10(139):58219. doi: 10.3791/58219.

Abstract

No effective treatments currently exist for placenta-associated pregnancy complications, and developing strategies for the targeted delivery of drugs to the placenta while minimizing fetal and maternal side effects remains challenging. Targeted nanoparticle carriers provide new opportunities to treat placental disorders. We recently demonstrated that a synthetic placental chondroitin sulfate A binding peptide (plCSA-BP) could be used to guide nanoparticles to deliver drugs to the placenta. In this protocol, we describe in detail a system for assessing the efficiency of drug delivery to the placenta by plCSA-BP that employs three separate methods used in combination: in vivo imaging, high-frequency ultrasound (HFUS), and high-performance liquid chromatography (HPLC). Using in vivo imaging, plCSA-BP-guided nanoparticles were visualized in the placentas of live animals, while HFUS and HPLC demonstrated that plCSA-BP-conjugated nanoparticles efficiently and specifically delivered methotrexate to the placenta. Thus, a combination of these methods can be used as an effective tool for the targeted delivery of drugs to the placenta and development of new treatment strategies for several pregnancy complications.

摘要

目前尚无针对胎盘相关妊娠并发症的有效治疗方法,开发在将胎儿和母体副作用降至最低的同时将药物靶向递送至胎盘的策略仍然具有挑战性。靶向纳米颗粒载体为治疗胎盘疾病提供了新的机会。我们最近证明,一种合成的胎盘硫酸软骨素A结合肽(plCSA-BP)可用于引导纳米颗粒将药物递送至胎盘。在本方案中,我们详细描述了一种通过plCSA-BP评估药物向胎盘递送效率的系统,该系统采用三种单独方法联合使用:体内成像、高频超声(HFUS)和高效液相色谱(HPLC)。使用体内成像,在活体动物的胎盘中可视化了plCSA-BP引导的纳米颗粒;而HFUS和HPLC表明,plCSA-BP偶联的纳米颗粒有效地将甲氨蝶呤特异性递送至胎盘。因此,这些方法相结合可作为将药物靶向递送至胎盘以及开发几种妊娠并发症新治疗策略的有效工具。

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