Transport of chitosan-DNA nanoparticles in human intestinal M-cell model versus normal intestinal enterocytes.
Transport of chitosan-DNA nanoparticles in human intestinal M-cell model versus normal intestinal enterocytes.
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DOI：
10.1016/j.ejps.2009.11.002
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发表时间：
2010-01-31
影响因子：
4.6
通讯作者：
Leong, Kam W.
中科院分区：
文献类型：
--
作者：
Kadiyala, Irina;Loo, Yihua;Roy, Krishnendu;Rice, Janet;Leong, Kam W.
口服疫苗是聚合物纳米颗粒最有前途的应用之一。使用两种不同的体外细胞模型来部分再现肠上皮细胞和M细胞的特征，本研究表明，纳米颗粒通过M细胞共培养模型的转运是肠上皮单层的5倍，至少80%的壳聚糖-DNA纳米颗粒在前30分钟内被摄取。在所研究的纳米颗粒的性质中，配体修饰对跨细胞率的影响最大：转铁蛋白修饰使通过这两种模型的转运增加了3-5倍。纳米颗粒的稳定性也影响着传输动力学。不稳定纳米粒子的因素，如低电荷(N/P)比和添加血清，会导致聚集，进而降低传输效率。在这些稳定性因素中，管腔pH值是非常重要的，因为pH从5.5增加到6.4和7.4会导致纳米颗粒传输分别下降3倍和10倍。由于可溶性壳聚糖可以作为促进剂，使细胞旁转运增加60%，这一下降部分归因于可溶性壳聚糖在接近中性的pH下沉淀。壳聚糖-DNA纳米颗粒在小肠的上部更稳定，这表明与回肠和结肠相比，十二指肠的摄取率可能更高。
Oral vaccination is one of the most promising applications of polymeric nanoparticles. Using two different in vitro cellular models to partially reproduce the characteristics of intestinal enterocytes and M-cells, this study demonstrates that nanoparticle transport through the M-cell co-culture model is 5 fold that of the intestinal epithelial monolayer, with at least 80% of the chitosan-DNA nanoparticles uptaken in the first 30 minutes. Among the properties of nanoparticles studied, ligand decoration has the most dramatic effect on the transcytosis rate: transferrin modification enhances transport through both models by 3–5 fold. The stability of the nanoparticles also affects transport kinetics. Factors which de-stabilize the nanoparticles, such as low charge (N/P) ratio and addition of serum, result in aggregation and in turn decreases transport efficiency. Of these stability factors, luminal pH is of great interest as an increase in pH from 5.5 to 6.4 and 7.4 leads to a 3 and 10 fold drop in nanoparticle transport respectively. Since soluble chitosan can act as an enhancer to increase paracellular transport by up to 60%, this decrease is partially attributed to the soluble chitosan precipitating near neutral pH. The implication that chitosan-DNA nanoparticles are more stable in the upper regions of the small intestine suggests that higher uptake rates may occur in the duodenum compared to the ileum and the colon.
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影响因子：
56.9
作者：
Kerneis, S;Bogdanova, A;Pringault, E
通讯作者：
Pringault, E
影响因子：
10.8
作者：
Leong, KW;Mao, HQ;August, JT
通讯作者：
August, JT
影响因子：
3.7
作者：
Desai, MP;Labhasetwar, V;Amidon, GL
通讯作者：
Amidon, GL
影响因子：
4.5
作者：
Jepson, Mark A.;Simmons, Nicholas L.;Hirst, Barry H.
通讯作者：
Hirst, Barry H.
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