Development and Characterization of Nanostructured Mists with Potential for Actively Targeting Poorly Water-Soluble Compounds into the Lungs
Development and Characterization of Nanostructured Mists with Potential for Actively Targeting Poorly Water-Soluble Compounds into the Lungs
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DOI：
10.1007/s11095-013-1088-2
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发表时间：
2013-10-01
影响因子：
3.7
通讯作者：
Kalinoski, Andrea L.
中科院分区：
文献类型：
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作者：
Nesamony, Jerry;Kalra, Ashish;Kalinoski, Andrea L.
为制备具有较好肺释药性能的纳米乳，筛选出由Cremophor RH 40、PEG 400和Labrafil M 2125 CS组成的自乳化纳米乳。在制剂组分中测试了水溶性差的药物卡马西平的溶解度。采用动态光散射、电泳光散射、透射电子显微镜（TEM）和差示扫描量热法对水包油（o/w）内斯进行了表征。使用商业雾化器将内斯雾化成雾，并使用激光衍射和TEM进行表征。建立了制备无菌内斯的无菌方法。采用MTT法评价了该制剂在NIH 3 T3细胞上的生物相容性。在斑马鱼卵、HeLa细胞和猪肺组织中测试制剂的体外渗透性。内斯具有小于20 nm大小的中性电荷液滴。雾化的内斯显示出o/w纳米结构。雾滴的尺寸小于5 μ m。无菌试验和细胞毒性结果证实NE具有生物相容性和无菌性。体外实验表明，纳米油滴可以穿透生物膜进入细胞内，这种纳米乳雾有可能作为水溶性差的药物的肺部给药系统。
To formulate nanoemulsions (NE) with potential for delivering poorly water-soluble drugs to the lungs.A self nanoemulsifying composition consisting of cremophor RH 40, PEG 400 and labrafil M 2125 CS was selected after screening potential excipients. The solubility of carbamazepine, a poorly water-soluble drug, was tested in the formulation components. Oil-in-water (o/w) NEs were characterized using dynamic light scattering, electrophoretic light scattering, transmission electron microscopy (TEM) and differential scanning calorimetry. NEs were nebulized into a mist using a commercial nebulizer and characterized using laser diffraction and TEM. An aseptic method was developed for preparing sterile NEs. Biocompatibility of the formulation was evaluated on NIH3T3 cells using MTT assay. In vitro permeability of the formulation was tested in zebra fish eggs, HeLa cells, and porcine lung tissue.NEs had neutrally charged droplets of less than 20 nm size. Nebulized NEs demonstrated an o/w nanostructure. The mist droplets were of size less than 5 mu m. Sterility testing and cytotoxicity results validated that the NE was biocompatible and sterile. In vitro tests indicated oil nanodroplets penetrating intracellularly through biological membranes.The nanoemulsion mist has the potential for use as a pulmonary delivery system for poorly water-soluble drugs.