BIOADHESIVE MICROSPHERES

我们建议开发基于微球的新型口服药物递送系统，该微球能够增加与粘液的生物粘附性。生物黏附现象被经典地归因于使用含有高浓度羧基的聚合物(据信与粘液形成氢键)和柔性聚合物链的存在(被认为可穿透生物结构)。我们发现，尽管缺乏柔性的高分子链，但疏水性生物可腐蚀性热塑性塑料表现出非常高的生物粘附性。热塑性生物粘附性最强的例子是聚酸酐共聚物。我们认为，粘附性的机制是降解过程中暴露出高密度的羧基，而其他表面亲水部分浓度较高的疏水聚合物将显示出很强的生物粘附性。我们的假设是，这些新型给药系统的性能可以通过使用四种不同的方法进行生物粘附力的体外测量来预测：外翻囊生物显微镜以及Cahn、EMFT和接触角研究的测量。这四种方法可以用来预测聚合物系统在大鼠和较大动物(猪)中的性能。最终目标是克服跨物种障碍，以加强我们的药物输送系统，用于人类。这项拟议研究的意义在于，它寻求将微球生物黏附基础研究得出的基本结果应用于开发新的药物输送系统，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传递系统从研究转移到临床应用，用于治疗疾病。

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.