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Solid lipid nanoparticles as a novel formulation approach for tanespimycin (17-AAG) against leishmania infections: Preparation, characterization and macrophage uptake.
Acta Tropica ( IF 2.7 ) Pub Date : 2020-06-23 , DOI: 10.1016/j.actatropica.2020.105595
Vinícius Couto Pires 1 , Carla Pires Magalhães 1 , Marcos Ferrante 2 , Juliana de Souza Rebouças 3 , Paul Nguewa 4 , Patrícia Severino 5 , Aldina Barral 1 , Patrícia Sampaio Tavares Veras 1 , Fabio Rocha Formiga 6
Affiliation  

17-N-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) is an inhibitor of heat shock protein 90 (Hsp90), which has been studied in the treatment of cancer such as leukemia or solid tumors. Alternatively, 17-AAG may represent a promising therapeutic agent against leishmaniasis. However, the delivery of 17-AAG is difficult due to its poor aqueous solubility. For exploring the therapeutic value of 17-AAG, we developed solid lipid nanoparticles (SLN) by double emulsion method. SLN exhibited ~100 nm, PDI < 0.2 and zeta potential ~20 mV. In addition, SLN were morphologically spherical with negligible aggregation. The entrapment efficiency of 17-AAG into the lipid matrix reached at nearly 80%. In a separate set of experiments, fluorescent SLN (FITC-labeled) showed a remarkable macrophage uptake, peaking within 2 h of incubation by confocal microscopy. Regarding the drug internalization as critical step for elimination of intracellular Leishmania, this finding demonstrates an important feature of the developed SLN. Collectively, these data indicate the feasibility of developing SLN as potential delivery systems for 17-AAG in leishmaniasis chemotherapy.



中文翻译:

固体脂质纳米颗粒作为坦尼斯霉素(17-AAG)对抗利什曼原虫感染的新型制剂方法:制备,表征和巨噬细胞摄取。

17-N-烯丙氨基-17-去甲氧基格尔德霉素(17-AAG,丹皮霉素)是热休克蛋白90(Hsp90)的抑制剂,已在癌症如白血病或实体瘤的治疗中进行了研究。或者,17-AAG可以代表有希望的抗利什曼病的治疗剂。然而,由于17-AAG的水溶性差,因此难以递送。为了探索17-AAG的治疗价值,我们通过双重乳液法开发了固体脂质纳米颗粒(SLN)。SLN表现出〜100 nm,PDI <0.2和Zeta电位〜20 mV。另外,SLN在形态学上是球形的,聚集可以忽略不计。17-AAG进入脂质基质的包封效率达到近80%。在另一组实验中,荧光SLN(FITC标记)显示出显着的巨噬细胞摄取,通过共聚焦显微镜在孵育后2小时内达到峰值。关于药物内化是消除细胞内的关键步骤利什曼原虫,这一发现证明了发达的SLN的重要特征。总的来说,这些数据表明开发SLN作为利什曼病化学治疗中潜在的17-AAG递送系统的可行性。

更新日期:2020-07-02
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