Synthesizing and characterizing novel designer microgels to address mucoadhesion

合成和表征新颖的设计微凝胶以解决粘膜粘附问题

• 批准号: 2750781
• 金额: --
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2750781
• 关键词: Synthesizing; characterizing; novel; designer; microgels

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.

最近，对设计粘膜粘附制剂的兴趣正在迅速增长，所述粘膜粘附制剂可用于预防和治疗粘膜的溃疡性、炎性和/或糜烂性病症和/或将药物活性化合物递送至粘膜表面以进行局部治疗或转移至体循环。通常，粘膜粘附是通过含有许多亲水基团的聚合物实现的，这些亲水基团在生理条件下强烈粘附到粘膜表面。这些聚合物可以延长通过各种粘膜给药途径（例如，口服、鼻内、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”，这是亚微米级的软水凝胶颗粒。它们的可调电荷分布使它们具有与粘膜非共价相互作用的模糊表面。除了静电之外，涉及它们通过与粘膜层的氢键结合充当胶的能力的粘附机制，加上它们的大的多孔内部结构以捕获活性物质和刺激响应性释放，应该使这些理想的粘膜粘附递送载体。尽管合成微凝胶对细胞的粘附长期以来一直是生物物理研究的焦点，但它们的粘膜粘附性能在很大程度上仍未被探索。这些阳离子微凝胶可以开辟新的令人兴奋的机会，由于它们的变形性，可调性，被困在各种配置的能力，从高度分散到压缩和紧密包装，当与各种表面相互作用。此外，用含有带电部分的线性/嵌段共聚物的系链官能化这种微凝胶的表面可以进一步锚定在粘膜内。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，并使用先进的实验和建模技术对其粘膜粘附特性进行新的理解，以应对各种生物粗糙度，变形性和润湿性表面。