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Hydrogels as novel substitutes of animal tissues for investigation of mucoadhesive properties of polymeric dosage forms

水凝胶作为动物组织的新型替代品用于研究聚合物剂型的粘膜粘附特性

基本信息

批准号：
BB/E003370/1
负责人：
Vitaliy Khutoryanskiy
金额：
$ 30.98万
依托单位：
University of Reading
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2007
资助国家：
英国
起止时间：
2007 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FE003370%2F1
关键词：
Hydrogels novel substitutes animal tissues

项目摘要

Mucous membranes line body cavities that are exposed to the external environment such as the respiratory tract, the gastrointestinal tract, the nostrils and the mouth. Mucus, secreted by glands and cells associated with the membrane, is a viscous yet slippery substance that mainly contains mucin, water and inorganic salts whose purpose is to act as a protective lubricant for the membrane. This viscous lining offers potential to adhere a pharmaceutical formulation to the membrane to allow prolonged drug delivery at a particular site; mucoadhesion can thus be defined as the adhesion of a formulation to a mucous membrane. In developing mucoadhesive drug delivery systems, the vast majority of researchers use animal tissue as a mimic for the human membranes. Over 60 % of research articles published in this area used animals which were sacrificed before or after the experiments. Also no standardised approach to using the animal membranes has been reported, and much work conflicts due the variations in animal model selected meaning the results from different laboratories may not be correlated. In this project, we will develop a standardised alternative synthetic 'mucous membrane mimic' which will be highly controlled and reproducible by forming hydrogel based on sugar based polymers. These glyco-polymers resemble the mucin and other components found in natural mucus and hydrogels, which are water swellable polymers that include a large fraction of water yet remain in a gel state, have been used to mimic other biological tissues. This project will synthesise a range of glycol-polymer hydrogels whose mucoadhesive properties will be validated by correlating adhesion of various formulations to the model in comparison with adhesion to pig mucosal membranes. By generating a standardised and validated model system, we will also be able to further investigate the mechanisms of mucoadhesion whilst offering a viable alternative to animal testing of these formulations.

粘膜排列在暴露于外部环境（例如呼吸道、胃肠道、鼻孔和口腔）的体腔内。粘液由与膜相关的腺体和细胞分泌，是一种粘性但光滑的物质，主要含有粘蛋白、水和无机盐，其目的是作为膜的保护性润滑剂。这种粘性衬里提供了将药物制剂粘附到膜上以允许在特定部位延长药物递送的可能性;因此，粘膜粘附可以定义为制剂粘附到粘膜上。在开发粘膜粘附给药系统中，绝大多数研究人员使用动物组织作为人类膜的模拟物。在这一领域发表的研究文章中，超过60%使用的动物在实验前后被处死。此外，还没有报告使用动物膜的标准化方法，并且由于所选动物模型的变化而导致许多工作冲突，这意味着来自不同实验室的结果可能不相关。在这个项目中，我们将开发一种标准化的替代合成“粘膜模拟物”，它将通过形成基于糖基聚合物的水凝胶来高度控制和再现。这些糖聚合物类似于天然粘液和水凝胶中发现的粘蛋白和其他组分，水凝胶是包括大部分水但仍保持凝胶状态的水可溶胀聚合物，已用于模拟其他生物组织。该项目将合成一系列二醇聚合物水凝胶，其粘膜粘附特性将通过将各种制剂与模型的粘附性与猪粘膜的粘附性进行比较来验证。通过生成标准化和验证的模型系统，我们还将能够进一步研究粘膜粘附的机制，同时为这些制剂的动物试验提供可行的替代方案。