Designing Highly Porous Drug-Impregnated Polymer Scaffolds Using Pressurized Gas Expanded Liquids for the Treatment of Lung Fibrosis and Wound Infections

基于其极高的比表面积，高孔材料在许多生物医学应用中具有显著的优势。特别是，对于低水溶性药物的输送，高孔道支架提供的高表面积为提高载药量提供了独特的机会，从而提高了药物治疗的有效性。然而，大多数用于制备此类支架的策略都非常缓慢和/或需要使用溶剂或其他添加剂，当材料在体内使用时可能会导致问题。我们的知识用户Ceapro(一家总部位于埃德蒙顿的生物技术公司)最近开发了一种名为加压气体膨胀液体(PGx)的高通量快速处理技术，除了提供对产生的材料的宏观尺寸(从大型连续网络到微观颗粒)以及内部孔隙大小的特殊控制外，该技术还克服了这些挑战。我们还合作开发了(1)通过对聚合物支架进行后处理和/或同时进行凝胶和PGx加工来将这些生物聚合物网络转化为水凝胶的方法，以及(2)通过简单且无残留溶剂的工艺来装载多种药物。在这个拟议的项目中，我们的目标是利用这些优势来应对治疗肺纤维化和感染伤口的关键挑战。对于肺纤维化，创造一种装载药物的高度多孔的微粒输送载体的可能性将提高基于吸入的治疗的效果；此外，Ceapro(β-葡聚糖)生产的一种关键生物聚合物提供理想的细胞靶向效果。对于伤口愈合，支架吸收渗出物和加载可调节的药物混合物的能力为提供协同药物组合治疗抗生素耐药感染提供了好处。总而言之，这项工作将利用一种获得专利的Cans，以应对加拿大人面临的新的健康挑战。

Highly porous materials offer significant advantages in many biomedical applications based on their extremely high surface areas. In particular, for the delivery of drugs with low water solubility, the high surface area provided by highly porous scaffolds offers unique opportunities for enhancing drug loading thus improving the efficacy of drug therapy.However, most strategies used to prepare such scaffolds are extremely slow and/or require the use of solvents or other additives that can cause issues when the material is used in the body. Our knowledge user Ceapro (a Edmonton-based biotechnology company) has recently developed a high-throughput and rapid processing technology called pressurized gas expanded liquids (PGX) that overcomes these challenges in addition to offering exceptional control over both the macroscopic size of the materials generated (from large continuous networks to microscale particles) as well as the size of the internal pores. We have also, in partnership, developed methods to (1) convert these biopolymer networks to hydrogels by post-processing the polymer scaffolds and/or performing gelation and PGX processing simultaneously and (2) load multiple drugs via a simple and residual solvent-free process. In this proposed project, we aim to exploit these advantages to address key challenges in treating lung fibrosis and infected wounds. For lung fibrosis, the potential to create a highly porous microparticle delivery vehicles loaded with drug would improve the efficacy of inhalation-based therapy; in addition, one of the key biopolymers produced by Ceapro (beta- glucan) provides desirable cell targeting effects. For wound healing, the capacity of the scaffolds to absorb exudate and load tunable mixtures of drugs offers benefits for delivering synergistic drug combinations to treat antibiotic-resistant infections. Together, this work will leverage a patented Canand emerging health challenges for Canadians.