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中性和阴离子多糖的流变学特性及其对黏液纤毛转运速率的影响

Rheological characterization of neutral and anionic polysaccharides with reduced mucociliary transport rates.

作者信息

Shah Ankur J, Donovan Maureen D

机构信息

Division of Pharmaceutics, University of Iowa, Iowa City, IA 52242, USA.

出版信息

AAPS PharmSciTech. 2007 Apr 20;8(2):Article 32. doi: 10.1208/pt0802032.

Abstract

The purpose of this research was to compare the viscoelastic properties of several neutral and anionic polysaccharide polymers with their mucociliary transport rates (MTR) across explants of ciliated bovine tracheal tissue to identify rheologic parameters capable of predicting the extent of reduction in mucociliary transport. The viscoelastic properties of the polymer gels and gels mixed with mucus were quantified using controlled stress rheometry. In general, the anionic polysaccharides were more efficient at decreasing the mucociliary transport rate than were the neutral polymers, and a concentration threshold, where no further decreases in mucociliary transport occurred with increasing polymer concentration, was observed for several of the neutral polysaccharides. No single rheologic parameter (eta, G', G'', tan delta, G*) was a good predictor of the extent of mucociliary transport reduction, but a combination of the apparent viscosity (eta), tangent to the phase angle (tan delta), and complex modulus (G*) was found to be useful in the identification of formulations capable of decreasing MTR. The relative values of each of the rheologic parameters were unique for each polymer, yet once the relationships between the rheologic parameters and mucociliary transport rate reduction were determined, formulations capable of resisting mucociliary clearance could be rapidly optimized.

摘要

本研究的目的是比较几种中性和阴离子多糖聚合物的粘弹性特性与其跨纤毛牛气管组织外植体的黏液纤毛运输速率(MTR),以确定能够预测黏液纤毛运输减少程度的流变学参数。使用控制应力流变仪对聚合物凝胶以及与黏液混合的凝胶的粘弹性特性进行了量化。总体而言,阴离子多糖比中性聚合物更有效地降低黏液纤毛运输速率,并且对于几种中性多糖观察到了一个浓度阈值,在该阈值以上,随着聚合物浓度增加,黏液纤毛运输不再进一步降低。没有单一的流变学参数(η、G'、G''、tanδ、G*)能够很好地预测黏液纤毛运输减少的程度,但发现表观粘度(η)、相位角正切值(tanδ)和复数模量(G*)的组合对于识别能够降低MTR的制剂很有用。每种流变学参数的相对值对于每种聚合物都是独特的,然而一旦确定了流变学参数与黏液纤毛运输速率降低之间的关系,就可以快速优化能够抵抗黏液纤毛清除的制剂。

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