Nanobody conjugated PLGA nanoparticles for active targeting of African Trypanosomiasis
Nanobody conjugated PLGA nanoparticles for active targeting of African Trypanosomiasis
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DOI：
10.1016/j.jconrel.2014.11.002
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发表时间：
2015-01-10
影响因子：
10.8
通讯作者：
Garcia-Salcedo, Jose A.
中科院分区：
文献类型：
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作者：
Arias, Jose L.;Unciti-Broceta, Juan D.;Garcia-Salcedo, Jose A.
靶向递送治疗剂是选择性治疗感染性疾病的替代方法。非洲锥虫是非洲锥虫病的病原体，其表面覆盖有由称为VSG的单一变体表面糖蛋白组成的表面涂层。该涂层通过内吞作用以非常高的速度回收，使得锥虫表面成为递送杀锥虫药物的极好靶点。在这里，我们报告了一种药物纳米载体的设计基于聚乙二醇（PEG）共价连接（PEG化）到聚（D，L-丙交酯-共-乙交酯酸）（PLGA），以产生PEG化的PLGA纳米颗粒。该纳米载体与特异性识别原生动物病原体布氏锥虫表面的单结构域重链抗体片段（纳米抗体）偶联。纳米颗粒负载有用于T. B.冈比亚急性感染。体外有效性试验显示，相对于游离药物，制剂的半抑制浓度（IC 50）降低了7倍。此外，使用非洲锥虫病小鼠模型的体内治疗表明，该制剂以比游离喷他脒的最小完全治愈剂量低10倍的剂量治愈了所有感染的小鼠，并且以低100倍的剂量治愈了60%的小鼠。这种纳米载体的设计包含了被批准用于人类的成分，并装载了目前用于治疗这种疾病的药物。此外，这种灵活的基于纳米抗体的系统可以适用于加载任何化合物，从而开辟了一系列新的潜在疗法，并可应用于其他疾病。(C)2014爱思唯尔有限公司版权所有。
Targeted delivery of therapeutics is an alternative approach for the selective treatment of infectious diseases. The surface of African trypanosomes, the causative agents of African trypanosomiasis, is covered by a surface coat consisting of a single variant surface glycoprotein, termed VSG. This coat is recycled by endocytosis at a very high speed, making the trypanosome surface an excellent target for the delivery of trypanocidal drugs. Here, we report the design of a drug nanocarrier based on poly ethylen glycol (PEG) covalently attached (PEGylated) to poly(D, L-lactide-co-glycolide acid) (PLGA) to generate PEGylated PLGA nanoparticles. This nanocarrier was coupled to a single domain heavy chain antibody fragment (nanobody) that specifically recognizes the surface of the protozoan pathogen Trypanosoma brucei. Nanoparticles were loaded with pentamidine, the first-line drug for T. b. gambiense acute infection. An in vitro effectiveness assay showed a 7-fold decrease in the half-inhibitory concentration (IC50) of the formulation relative to free drug. Furthermore, in vivo therapy using a murine model of African trypanosomiasis demonstrated that the formulation cured all infected mice at a 10-fold lower dose than the minimal full curative dose of free pentamidine and 60% of mice at a 100-fold lower dose. This nanocarrier has been designed with components approved for use in humans and loaded with a drug that is currently in use to treat the disease. Moreover, this flexible nanobody-based system can be adapted to load any compound, opening a range of new potential therapies with application to other diseases. (C) 2014 Elsevier B.V. All rights reserved.