BIOADHESIVE MICROSPHERES

生物粘附微球

基本信息

批准号：
6179412
负责人：
Edith Mathiowitz
金额：
$ 29.25万
依托单位：
BROWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-05-01 至 2003-06-30
项目状态：
已结题

项目摘要

We propose to develop novel oral drug delivery systems based on microspheres capable of increased bioadhesion with mucus. The bioadhesive phenomenon has been classically attributed to the use of polymers containing high concentrations of carboxyl groups (believed to form hydrogen bonds with mucus) and the presence of flexible polymer chains (thought to interpenetrate biological structures). We found that hydrophobic bioerodible thermoplastics exhibit very high bioadhesive -properties despite the lack of flexible polymer chains. The strongest example of thermoplastic bioadhesion occurred with polyanhydride copolymers. We believe the mechanism for adhesion is the high density of carboxylic groups exposed during degradation, and that other hydrophobic polymers with high concentrations of surface hydrophilic moieties will exhibit strong bioadhesive measurements. It is our hypothesis that performance of these novel drug delivery systems can be predicted by in vitro measurements of bioadhesive forces using four different methods: everted sac biaossay and measurements from CAHN, EMFT and contact angle studies. The four methods can be utilized to predict the performance of polymer systems in both rats and in larger animals (pigs). The end goal is to overcome the trans-species barrier in order to potentiate our drug delivery systems for use in humans. The significance of the proposed research is that it seeks to apply fundamental findings, derived from basic research into microsphere bioadhesion, to the development of new drug delivery systems and apply this to in vivo experiments in different species. The end goal is to move these novel drug delivery systems from research to clinical applications for treatment of diseases.

我们建议基于能够增加粘液生物粘附的微球开发新的口服药物输送系统。生物粘附现象经典归因于使用含有高浓度的羧基（认为与粘液形成氢键的聚合物）以及存在柔性聚合物链（被认为是介育生物学结构）。我们发现，尽管缺乏柔性聚合物链，但疏水性生物剂的热塑性塑料表现出非常高的生物粘附性效果。聚苯基共聚物发生的热塑性生物粘附的最强例子。我们认为，粘附的机制是在降解过程中暴露的羧基的高密度，并且其他具有高浓度表面亲水性部分的疏水聚合物将表现出强大的生物粘合度测量。我们的假设是，可以使用四种不同的方法在体外测量生物粘附力的体外测量来预测这些新型药物输送系统的性能：经过的SAC Biaossay和CAHN，EMFT和接触角研究的测量。可以利用这四种方法来预测大鼠和大动物（猪）中聚合物系统的性能。最终目标是克服跨物种障碍，以增强我们在人类中使用的药物输送系统。拟议的研究的重要性是，它试图将基本研究从微球生物粘附中得出的基本发现应用于新药递送系统的开发，并将其应用于不同物种的体内实验。最终目标是将这些新型药物输送系统从研究转移到治疗疾病的临床应用。