Engineering Bacteria-Responsive Intravaginal Rings for Controlled Drug Delivery

工程细菌响应阴道环用于控制药物输送

• 批准号: RGPIN-2021-03072
• 负责人: Ho, Emmanuel
• 金额: $ 2.4万
• 依托单位: University of Waterloo
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=742363
• 关键词: Engineering; Bacteria; Responsive; Intravaginal; Rings

Major advantage of implants is their ability to provide long-term drug delivery. Current intravaginal implants such as intravaginal rings (IVRs) and intrauterine devices rely on simple drug diffusion for drug delivery. The method of fabrication results in a matrix-based system that only allows diffusion of small molecule drugs from the polymer. Based on these current designs, it would not be possible to deliver nucleic acids, proteins/peptides, or nanocarrier systems from the implant systems. A major challenge in the materials science field is the development of precisely tuned stimuli-responsive drug delivery systems that can produce predictable drug release rates. As a result, the proposed research program is focused on the development of advanced biomaterials for the fabrication of bacteria-responsive IVRs that will provide controlled sustained delivery of antibiotic-encapsulated nanoparticles for >14 days. Initial focus will be on the fabrication of IVRs synthesized from novel polyurethane composite biomaterials that alter its composition in the presence of specific bacterial enzymes. These IVRs are designed to respond to changes to the microflora environment of the female genital tract e.g. little to no drug release at normal physiological conditions and rapid drug release when specific enzymes are released by foreign bacteria. Physical-chemical characterization of the newly synthesized biomaterials will be performed to determine properties such as melting temperature, porosity, shore hardness, etc. The influence of these various properties on the structural features of the fabricated IVRs and its impact on the release profile of antibiotic-encapsulated nanoparticles will also be investigated. The implant drug delivery system will be evaluated for biocompatibility, its ability to release drug in the presence of specific bacteria, long-term stability, and efficacy in reducing bacterial growth. Overall, the proposed research program is innovative and will significantly contribute to the advancement of knowledge in the field of materials science, via the generation of novel bacteria-responsive polyurethane composite biomaterials for the controlled delivery of nanoparticles. Most importantly, highly qualified personnel trained in this research program will acquire the necessary knowledge and skills to be leaders in the fields of biopolymers, materials engineering, and drug delivery.

植入物的主要优点是它们提供长期药物递送的能力。目前的阴道内植入物如阴道内环（IVRs）和宫内节育器依赖于简单的药物扩散来进行药物递送。该制造方法产生基于基质的系统，其仅允许小分子药物从聚合物扩散。基于这些当前设计，不可能从植入物系统递送核酸、蛋白质/肽或纳米载体系统。材料科学领域的一个主要挑战是开发能够产生可预测药物释放速率的精确调谐的刺激响应药物递送系统。因此，拟议的研究计划侧重于开发用于制造细菌响应性IVRs的先进生物材料，这些生物材料将提供>14天的药物封装纳米颗粒的受控持续递送。最初的重点将是制造由新型聚氨酯复合生物材料合成的IVR，该材料在特定细菌酶的存在下改变其组成。这些IVR旨在对女性生殖道微生物群落环境的变化做出反应，例如，在正常生理条件下很少或没有药物释放，以及当外源细菌释放特定酶时快速释放药物。将进行新合成的生物材料的物理化学表征，以确定属性，如熔化温度，孔隙率，海岸硬度等。这些不同的属性对制造的IVRs的结构特征的影响及其对药物包封的纳米颗粒的释放曲线的影响也将进行研究。将评价植入药物递送系统的生物相容性、在特定细菌存在下释放药物的能力、长期稳定性和减少细菌生长的有效性。总体而言，拟议的研究计划具有创新性，将通过产生用于纳米颗粒受控递送的新型细菌响应性聚氨酯复合生物材料，为材料科学领域的知识进步做出重大贡献。最重要的是，在这项研究计划中培训的高素质人员将获得必要的知识和技能，成为生物聚合物，材料工程和药物输送领域的领导者。