The impact of AT1002 on the delivery of ritonavir in the presence of bioadhesive polymer, carrageenan.
The impact of AT1002 on the delivery of ritonavir in the presence of bioadhesive polymer, carrageenan.
复制标题
在生物粘附聚合物角叉菜胶存在的情况下，AT1002 对利托那韦递送的影响。
DOI：
10.1007/s12272-012-0520-1
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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
理论上，对紧密连接修饰的新见解提供了调节扩散屏障的机会，从而使研究低生物利用度治疗药物的渗透增强剂成为可能。AT 1002是闭合小带毒素的最小生物活性片段，与Zonulin受体结合后可逆地打开细胞间紧密连接，增加了各种分子量标记物或低生物利用度药物的转运。本研究的目的是连续评价鼻内给予抗逆转录病毒药物利托那韦后，在生物粘附剂角叉菜胶存在下AT 1002的渗透增强能力，以及与先前结果相比的渗透增强率。生物粘附剂卡拉胶可显著促进AT 1002的促渗作用。与对照组相比，利托那韦与AT 1002和角叉菜胶联合给药导致AUC 0 - 240 min增加2.55倍，Cmax增加2.48倍。然而，AT 1002在不存在角叉菜胶的情况下没有产生利托那韦吸收的统计学增强。因此，AT 1002与卡拉胶的加入一起可能开辟紧密连接调节渗透促进剂的新研究途径，并允许开发治疗剂的粘膜给药。
New insights into the modification of the tight junctions theoretically offer the opportunity to regulate the diffusion barrier and then make it possible to investigate a permeation enhancer of low-bioavailability therapeutic agents. AT1002, a minimum biologically active fragment ofzonula occludenstoxin which reversibly opens intercellular tight junctions after binding to the Zonulin receptor, increased the transport of various molecular weight markers or low-bioavailability agents. The objective of this study was continuously to evaluate the permeationenhancing ability of AT1002 in the presence of the bioadhesive agent, carrageenan after intranasal administration of the antiretroviral drug, ritonavir, and the permeation enhancement ratio compared with the previous results. The permeation-enhancing effect of AT1002 was significantly promoted by the bioadhesive agent, carrageenan. The administration of ritonavir with AT1002 and carrageenan resulted in a 2.55-fold increase in AUC0–240minand a 2.48-fold increase in Cmaxcompared with the control group. However, AT1002 in the absence of carrageenan did not produce a statistic enhancement in the absorption of ritonavir. Hence, AT1002 together with the addition of carrageenan may open a new approach of research in the tight junction modulated permeation enhancer, and allow the development of the mucosal drug delivery of therapeutic agents.