BIOADHESIVE MICROSPHERES

我们建议开发基于微球的新型口服给药系统，该系统能够增加与粘液的生物粘附性。生物粘附现象通常归因于使用含有高浓度羧基的聚合物（被认为与粘液形成氢键）和柔性聚合物链的存在（被认为可以穿透生物结构）。我们发现疏水生物可降解热塑性塑料尽管缺乏柔性聚合物链，但仍表现出非常高的生物粘附性能。热塑性生物粘附最强的例子发生在聚酸酐共聚物上。我们认为黏附的机制是在降解过程中暴露的高密度羧基，而其他具有高浓度表面亲水性部分的疏水聚合物将表现出很强的生物黏附测量。我们的假设是，这些新型药物输送系统的性能可以通过使用四种不同的方法来预测生物粘附力的体外测量：外转囊生物印迹和CAHN、EMFT和接触角研究的测量。这四种方法可用于预测聚合物体系在大鼠和大型动物（猪）中的性能。最终目标是克服跨物种障碍，以增强我们的药物输送系统用于人类。拟议研究的意义在于，它寻求将来自微球生物粘附基础研究的基础发现应用于新的药物传递系统的开发，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疾病治疗的临床应用。

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.