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PLGA nanocapsules improve the delivery of clarithromycin to kill intracellular Staphylococcus aureus and Mycobacterium abscessus.
Nanomedicine: Nanotechnology, Biology and Medicine ( IF 4.2 ) Pub Date : 2019-11-18 , DOI: 10.1016/j.nano.2019.102125
Frantiescoli Anversa Dimer 1 , Cristiane de Souza Carvalho-Wodarz 1 , Adriely Goes 2 , Katarina Cirnski 3 , Jennifer Herrmann 3 , Viktoria Schmitt 3 , Linda Pätzold 4 , Nadia Abed 5 , Chiara De Rossi 1 , Markus Bischoff 4 , Patrick Couvreur 5 , Rolf Müller 3 , Claus-Michael Lehr 2
Affiliation  

Drug delivery systems are promising for targeting antibiotics directly to infected tissues. To reach intracellular Staphylococcus aureus and Mycobacterium abscessus, we encapsulated clarithromycin in PLGA nanocapsules, suitable for aerosol delivery by nebulization of an aqueous dispersion. Compared to the same dose of free clarithromycin, nanoencapsulation reduced 1000 times the number of intracellular S. aureus in vitro. In RAW cells, while untreated S. aureus was located in acidic compartments, the treated ones were mostly situated in non-acidic compartments. Clarithromycin-nanocapsules were also effective against M. abscessus (70-80% killing efficacy). The activity of clarithromycin-nanocapsules against S. aureus was also confirmed in vivo, using a murine wound model as well as in zebrafish. The permeability of clarithromycin-nanocapsules across Calu-3 monolayers increased in comparison to the free drug, suggesting an improved delivery to sub-epithelial tissues. Thus, clarithromycin-nanocapsules are a promising strategy to target intracellular S. aureus and M. abscessus.

中文翻译:

PLGA纳米胶囊改善了克拉霉素的递送,以杀死细胞内金黄色葡萄球菌和脓肿分枝杆菌。

药物输送系统有望将抗生素直接靶向感染的组织。为了达到胞内金黄色葡萄球菌和脓肿分枝杆菌,我们将克拉霉素封装在PLGA纳米胶囊中,适合通过雾化水分散液来进行气雾剂递送。与相同剂量的游离克拉霉素相比,体外纳米封装减少了细胞内金黄色葡萄球菌数量的1000倍。在RAW细胞中,未处理的金黄色葡萄球菌位于酸性隔室中,而处理过的金黄色葡萄球菌大多位于非酸性隔室中。克拉霉素纳米球对脓肿分支杆菌也有效(70-80%的杀灭效力)。使用鼠伤模型以及在斑马鱼中,在体内也证实了克拉霉素纳米胶囊对金黄色葡萄球菌的活性。与游离药物相比,克拉霉素纳米胶囊跨Calu-3单层的渗透性增加,表明向上皮下组织的递送有所改善。因此,克拉霉素纳米球囊泡是靶向细胞内金黄色葡萄球菌和脓性支原体的有前途的策略。
更新日期:2019-11-19
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