Synthesizing and characterizing novel designer microgels to address mucoadhesion

近年来，人们对设计用于预防和治疗粘膜溃烂、炎症和/或腐蚀性疾病和/或将药物活性化合物输送到粘膜表面进行局部治疗或转移到体循环的粘附剂制剂的兴趣日益浓厚。通常，粘附性是通过含有大量亲水性基团的聚合物实现的，这些亲水性基团在生理条件下强烈地附着在粘膜表面。这些聚合物可以延长通过各种粘膜给药途径(如口服、鼻腔、阴道)传递的活性物质的停留时间。我们提出了一种新型的软固体，即微凝胶，这是一种亚微米大小的软水凝胶颗粒。它们可调节的电荷分布使它们有一个模糊的表面，可以与粘膜非共价相互作用。除了静电学，粘附性机制包括它们通过与粘膜层氢键起胶水作用的能力，以及它们大孔的内部结构，以捕获活性和刺激反应特性以释放，这应该使这些理想的粘附性输送载体成为理想的粘附性递送载体。虽然合成微凝胶与细胞的黏附一直是生物物理研究的焦点，但它们的黏附性能在很大程度上仍未被探索。这些阳离子微凝胶由于其可变形、可调谐、能够被捕获在各种构型中，从高度分散到压缩和紧密堆积，当与各种表面相互作用时，可能会打开新的令人兴奋的机会。此外，用含有带电部分的线状/嵌段共聚物系链对这种微凝胶表面进行功能化处理，可以进一步促进粘膜内的锚定。在这个博士项目中，我们建议设计具有靶向结构的新型微凝胶，并利用先进的实验和建模技术对其粘附性特性进行新的理解，以响应生物粗糙度、可变形性和润湿性的不同表面。

There is burgeoning recent interest in designing mucoadhesive formulations which are useful for the prevention and treatment of ulcerative, inflammatory, and/or erosive disorders of mucous membranes and/or the delivery of pharmaceutically active compounds to mucosal surfaces for topical treatment or transfer to the systemic circulation. Often mucoadhesion is achieved by polymers containing numerous hydrophilic groups that adhere strongly to mucosal surfaces under physiological conditions. These polymers can extend the residence time of actives delivered through various mucosal administration routes (e.g. oral, nasal, vaginal). We propose a novel class of soft solids, "microgels", which are sub-micron-sized soft hydrogel particles. Their tuneable charge distribution gives them a fuzzy surface to interact non-covalently with mucosa. Beyond electrostatics, the adhesive mechanism involving their ability to act as glue via hydrogen bonding with mucosal layers coupled with their large porous internal structure to entrap actives and stimuli-responsive properties for release should make these ideal mucoadhesive delivery vehicles. Although the adhesion of synthetic microgels to cells has long been a focus of biophysical research, their mucoadhesive performance has remained largely unexplored. These cationic microgels may open up new exciting opportunities due to their deformability, tunability, ability to be trapped in various configurations, from highly spread to compressed and close packed, when interacting with various surfaces. In addition, functionalizing the surface of such microgels with tethers of linear/ block copolymers containing charged moieties could further the anchoring within the mucosa. In this PhD project, we propose to design novel microgels with targeted architecture and create a new understanding of their mucoadhesive properties in response to various surfaces of biological roughness, deformability and wettability using advanced experimental as well as modelling techniques.