Department of Large Animal Clinical Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
Int J Nanomedicine. 2009;4:289-97. doi: 10.2147/ijn.s7137. Epub 2009 Dec 29.
Pluronic based core-shell nanostructures encapsulating gentamicin were designed in this study. Block copolymers of (PAA(+/-)Na-b-(PEO-b-PPO-b-PEO)-b-PAA(+/-)Na) were blended with PAA(-) Na(+) and complexed with the polycationic antibiotic gentamicin to form nanostructures. Synthesized nanostructures had a hydrodynamic diameter of 210 nm, zeta potentials of -0.7 (+/-0.2), and incorporated approximately 20% by weight of gentamicin. Nanostructures upon co-incubation with J774A.1 macrophage cells showed no adverse toxicity in vitro. Nanostructures administered in vivo either at multiple dosage of 5 microg g(-1) or single dosage of 15 microg g(-1) in AJ-646 mice infected with Salmonella resulted in significant reduction of viable bacteria in the liver and spleen. Histopathological evaluation for concentration-dependent toxicity at a dosage of 15 microg g(-1) revealed mineralized deposits in 50% kidney tissues of free gentamicin-treated mice which in contrast was absent in nanostructure-treated mice. Thus, encapsulation of gentamicin in nanostructures may reduce toxicity and improve in vivo bacterial clearance.
本研究设计了包载庆大霉素的基于普朗尼克的核壳纳米结构。（PAA(+/-)Na-b-(PEO-b-PPO-b-PEO)-b-PAA(+/-)Na）嵌段共聚物与 PAA(-)Na(+)混合，并与多阳离子抗生素庆大霉素络合形成纳米结构。合成的纳米结构具有 210nm 的水动力直径、-0.7(+/-0.2)的 zeta 电位，并且约含有 20%重量的庆大霉素。纳米结构与 J774A.1 巨噬细胞共同孵育在体外没有显示出任何毒性。在感染沙门氏菌的 AJ-646 小鼠中，以 5μg g(-1)的多次剂量或 15μg g(-1)的单次剂量给予纳米结构，在体内均导致肝脏和脾脏中存活细菌数量显著减少。在 15μg g(-1)剂量下进行的浓度依赖性毒性的组织病理学评价显示，在未用纳米结构处理的小鼠中，50%的肾组织中有矿化沉积物，而在自由庆大霉素处理的小鼠中则没有。因此，将庆大霉素包封在纳米结构中可能会降低毒性并提高体内细菌清除率。
