期刊
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
卷 56, 期 2, 页码 207-214出版社
ELSEVIER
DOI: 10.1016/S0939-6411(03)00061-4
关键词
mucin; poly(acrylic acid); thiomers; rheology; disulphide bonds
Disulphide bonds between thiolated polymers (thiomers) and cysteine-rich subdomains of mucus glycoproteins are supposed to be responsible for the enhanced mucoadhesive properties of thiomers. This study set out to provide evidence for these covalent interactions using poly(acrylic acid)-cysteine conjugates of 2 and 450 kDa (PAA(2)-Cys, PAA(450)-Cys) displaying 402.5-776.0 mumol thiol groups per gram polymer. The effect of the disulphide bond breaker cysteine on thiomer-mucin disulphide bonds was monitored by (1) mucoadhesion studies and (2) rheological studies. Furthermore, (3) diffusion studies and (4) gel filtration studies were performed with thiomer-mucus mixtures. The addition of cysteine significantly (P < 0.01) reduced the adhesion of thiomer tablets to porcine mucosa and G'/G values of thiomer-mucin mixtures, whereas unthiolated controls were not influenced. These results indicate the cleavage of disulphide bonds between thiomer and mucus glycoproteins. Diffusion studies demonstrated that a 12.8-fold higher concentration of the thiomer (PAA(2)-Cys) remains in the mucin gel than the corresponding unmodified polymer. Gel filtration studies showed that PAA(2)-Cys was able to form disulphide bonds with mucin glycoproteins resulting in an altered elution profile of the mucin/PAA(2)-Cys mixture in comparison to mucin alone or mucin/PAA(2) mixture. According to these results, the study provides evidence for the formation of covalent bonds between thiomer and mucus glycoproteins. (C) 2003 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据