Synthesizing and characterizing novel designer microgels to address mucoadhesion

最近，人们对设计黏附制剂的兴趣日益浓厚，这种制剂可用于预防和治疗溃疡性、炎症性和/或粘膜侵蚀性疾病和/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。通常黏附是由含有大量亲水性基团的聚合物在生理条件下强烈粘附在粘膜表面实现的。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）递送的活性物质的停留时间。我们提出了一类新的软固体，“微凝胶”，这是亚微米大小的软水凝胶颗粒。它们可调节的电荷分布使其具有模糊的表面以与粘膜非共价相互作用。除了静电之外，它们的粘附机制包括通过与粘膜层的氢键作用充当胶水的能力，再加上它们的大多孔内部结构可以捕获活性物质和刺激响应特性以释放，这应该使它们成为理想的黏合剂输送载体。尽管合成微凝胶与细胞的粘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。这些阳离子微凝胶在与各种表面相互作用时，由于其可变形性、可调节性、可被困在各种构型（从高度扩散到压缩和紧密排列）中，可能会开辟新的令人兴奋的机会。此外，用含有带电基团的线状/嵌段共聚物的系绳使这种微凝胶的表面功能化可以进一步在粘膜内锚定。在这个博士项目中，我们建议设计具有目标结构的新型微凝胶，并利用先进的实验和建模技术，对它们在各种生物粗糙度、可变形性和可润湿性表面上的粘接特性有新的认识。

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.