Shape effect in the design of nanowire-coated microparticles as transepithelial drug delivery devices.
Shape effect in the design of nanowire-coated microparticles as transepithelial drug delivery devices.
复制标题
DOI：
10.1021/nn3019865
复制
发表时间：
2012-09-25
期刊：
影响因子：
17.1
通讯作者：
Desai, Tejal A.
中科院分区：
文献类型：
--
作者：
Uskokovic, Vuk;Lee, Kunwoo;Lee, Phin Peng;Fischer, Kathleen E.;Desai, Tejal A.
虽然口服给药途径传统上在患者中最受欢迎，但据估计，90%的治疗性化合物具有口服生物利用度限制。因此，开发新型药物载体以更有效地口服治疗药物是一个重要的目标。通过在狭窄分散的微米硅珠表面生长纳米硅线制成的复合颗粒以前被证明能够：(A)通过将纳米线与顶端微绒毛交错排列，很好地附着在上皮上；以及(B)增加Caco-2细胞单层相对于小有机分子的渗透性，与它们的浓度成正比。本研究的主题是比较球形和平面颗粒形态在体外和体内对上皮细胞层通透性的影响。由于其更大的表面积，平面颗粒比球形颗粒表现出更高的载药效率，同时增加了中等尺寸模型药物胰岛素的跨皮渗透。平面纳米线包裹颗粒的胰岛素释放曲线显示药物累积释放量持续增加，在1-4h的洗脱时间内接近恒定的释放速率。一项免疫组织化学研究证实，与球形颗粒相比，包裹着纳米线的平面二氧化硅颗粒能够更大程度地松开上皮细胞的紧密连接，从而使药物能够更容易地通过上皮运输。对大小从0.4 kDa到150 kDa的模型药物进行的跨皮渗透测试产生了三类分子，这取决于它们的渗透倾向。胰岛素属于只有在纳米线包裹的颗粒的帮助下才能通过上皮释放的分子。其他药物组，分别是较小的和较大的，要么不需要载体渗透上皮，要么即使有纳米线涂层颗粒的支持也无法穿过它。口服胰岛素在兔体内的生物利用度也被发现，当与纳米线涂层的平面颗粒一起给药时，生物利用度提高。
While the oral drug delivery route has traditionally been the most popular among patients, it is estimated that 90 % of therapeutic compounds possess oral bioavailability limitations. Thus, the development of novel drug carriers for more effective oral delivery of therapeutics is an important goal. Composite particles made by growing nanoscopic silicon wires from the surface of narrowly dispersed, microsized silica beads were previously shown to be able to: (a) adhere well onto the epithelium by interdigitating their nanowires with the apical microvilli; and (b) increase the permeability of Caco-2 cell monolayers with respect to small organic molecules in direct proportion to their concentration. A comparison between the effects of spherical and planar particle morphologies on the permeability of the epithelial cell layer in vitro and in vivo presented the subject of this study. Owing to their larger surface area, the planar particles exhibited a higher drug loading efficiency than their spherical counterparts, while simultaneously increasing the transepithelial permeation of a moderately sized model drug, insulin. The insulin elution profile for planar nanowire-coated particles displayed a continual increase in the cumulative amount of the released drug, approaching a constant release rate for 1 – 4 h period of the elution time. An immunohistochemical study confirmed the ability of planar silica particles coated with nanowires to loosen the tight junction of the epithelial cells to a greater extent than the spherical particles did, thus enabling a more facile transport of the drug across the epithelium. Transepithelial permeability tests conducted for model drugs ranging in size from 0.4 to 150 kDa yielded three categories of molecules depending on their permeation propensities. Insulin belonged to the category of molecules deliverable across the epithelium only with the assistance of nanowire-coated particles. Other groups of drugs, smaller and bigger, respectively, either did not need the carrier to permeate the epithelium or were not able to cross it even with the support from the nanowire-coated particles. Bioavailability of insulin orally administered to rabbits was also found to be increased when delivered in conjunction with the nanowire-coated planar particles.
登录
查看更多内容
影响因子：
3.5
作者：
Sander, GR;Cummins, AG;Powell, BC
通讯作者：
Powell, BC
DOI：
10.1016/j.nano.2010.12.007
发表时间：
2011-08-01
影响因子：
5.4
作者：
Neumeyer, Andrea;Bukowski, Mirko;Daum, Nicole
通讯作者：
Daum, Nicole
影响因子：
2.4
作者：
CLAUDE, P
通讯作者：
CLAUDE, P
影响因子：
3.8
作者：
Behrens, I;Kamm, W;Kissel, T
通讯作者：
Kissel, T
DOI：
10.1016/0006-291x(91)91647-u
发表时间：
1991-03-29
影响因子：
3.1
作者：
ARTURSSON, P;KARLSSON, J
通讯作者：
KARLSSON, J