The influence of stabilizer and bioadhesive polymer on the permeation-enhancing effect of AT1002 in the nasal delivery of a paracellular marker.
The influence of stabilizer and bioadhesive polymer on the permeation-enhancing effect of AT1002 in the nasal delivery of a paracellular marker.
复制标题
稳定剂和生物粘附聚合物对 AT1002 在鼻腔递送旁细胞标记物中渗透增强作用的影响。
DOI：
10.1007/s12272-012-0217-5
复制
发表时间：
2012
影响因子：
6.7
通讯作者：
Eddington,NatalieD
中科院分区：
文献类型：
--
作者：
Song,Keon-Hyoung;Eddington,NatalieD
渗透促进剂主要用于改善由于膜渗透性差而导致的治疗剂的低生物利用度。AT 1002是封闭带毒素的一个6氨基酸片段，据报道具有渗透促进作用。然而，建议进一步研究关注AT 1002的肽性质，如稳定性和膜清除率，以准确反映其渗透增强潜力。因此，本文重点关注了AT 1002对识别添加剂的敏感性，以最大限度地降低AT 1002的不稳定性，以及AT 1002与生物粘附聚合物联合给药时的渗透增强作用。稳定性研究表明，AT 1002在中性至碱性pH条件下不稳定，并且随着孵育时间的增加，5%葡萄糖和1%氨基酸（精氨酸、半胱氨酸、甘氨酸）混合物分别在pH 7.4下至少6小时内显著降低了AT 1002的不稳定性。在细胞旁标志物的鼻内研究中，与对照组相比，在存在角叉菜胶的情况下，甘露醇与AT 1002的5%葡萄糖溶液给药导致Cmax和AUC 0 - 360 min统计学显著性增加3.14倍和2.17倍。因此，添加角叉菜胶作为生物粘附性聚合物和葡萄糖作为稳定剂与AT 1002一起可以允许开发低生物利用度治疗剂的粘膜药物递送。
Permeation enhancers are of major interest to improve the low bioavailability of therapeutic agents due to poor membrane permeation. AT1002, a six-amino acid fragment of Zonula occludens toxin, was reported to possess permeation-enhancing effects. However, further studies were suggested to focus on the peptide nature of AT1002 like stability and membrane clearance to accurately reflect its permeation-enhancing potential. Thus, this paper focused on the susceptibility of AT1002 for identifying additives to minimize the instability of AT1002, and the permeation-enhancing effect of AT1002 when co-administered with a bioadhesive polymer. The stability study showed that AT1002 were unstable in neutral to basic pH conditions and with increasing incubation time, and 5% dextrose and the 1% mixture of amino acids (arginine, cysteine, glycine) significantly minimized the instability of AT1002 at pH 7.4 for at least 6 hours, respectively. In the intranasal study of a paracellular marker, the administration of mannitol with AT1002 in 5% dextrose solution led to statistically significant 3.14- and 2.17-fold increases in Cmaxand AUC0-360minin the presence of carrageenan over the control. Thus, the addition of carrageenan as a bioadhesive polymer and dextrose as a stabilizer together with AT1002 may allow the development of the mucosal drug delivery of low-bioavailability therapeutic agents.