Departamento de Química Orgánica-Institute of Nanoscience of Aragon (INA), University of Zaragoza, Pedro Cerbuna 12, ES-50009 Zaragoza, Spain.
Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), Baldiri Reixac 10-12, ES-08028 Barcelona, Spain; Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), Rosselló 149-153, ES-08036 Barcelona, Spain.
Biomaterials. 2014 Sep;35(27):7940-50. doi: 10.1016/j.biomaterials.2014.05.061. Epub 2014 Jun 13.
It can be foreseen that in a future scenario of malaria eradication, a varied armamentarium will be required, including strategies for the targeted administration of antimalarial compounds. The development of nanovectors capable of encapsulating drugs and of delivering them to Plasmodium-infected cells with high specificity and efficacy and at an affordable cost is of particular interest. With this objective, dendritic derivatives based on 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) and Pluronic(®) polymers have been herein explored. Four different dendritic derivatives have been tested for their capacity to encapsulate the antimalarial drugs chloroquine (CQ) and primaquine (PQ), their specific targeting to Plasmodium-infected red blood cells (pRBCs), and their antimalarial activity in vitro against the human pathogen Plasmodium falciparum and in vivo against the rodent malaria species Plasmodium yoelii. The results obtained have allowed the identification of two dendritic derivatives exhibiting specific targeting to pRBCs vs. non-infected RBCs, which reduce the in vitro IC50 of CQ and PQ by ca. 3- and 4-fold down to 4.0 nm and 1.1 μm, respectively. This work on the application of dendritic derivatives to antimalarial targeted drug delivery opens the way for the use of this new type of chemicals in future malaria eradication programs.
可以预见，在未来的疟疾消除情景中，需要各种手段，包括针对抗疟化合物靶向给药的策略。特别感兴趣的是开发能够包封药物并以高特异性和有效性、且价格合理的方式将其递送至感染疟原虫的细胞的纳米载体。为此，本文探索了基于 2,2-双（羟甲基）丙酸（bis-MPA）和 Pluronic(®)聚合物的树突状衍生物。测试了四种不同的树突状衍生物包封抗疟药物氯喹（CQ）和伯氨喹（PQ）的能力、对感染疟原虫的红细胞（pRBC）的特异性靶向作用，以及它们在体外对人类病原体恶性疟原虫和体内对啮齿动物疟原虫种约氏疟原虫的抗疟活性。所得结果鉴定出两种树突状衍生物对 pRBC 与未感染 RBC 具有特异性靶向作用，将 CQ 和 PQ 的体外 IC50 分别降低约 3 倍和 4 倍，达到 4.0nm 和 1.1μm。这项关于树突状衍生物在抗疟靶向药物传递中应用的工作为在未来的疟疾消除计划中使用这种新型化学物质开辟了道路。
