Engineering Bacteria-Responsive Intravaginal Rings for Controlled Drug Delivery

植入物的主要优点是它们能够提供长期的药物输送。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给药。制造方法产生的基于基质的系统只允许小分子药物从聚合物中扩散。基于这些目前的设计，不可能从植入系统中递送核酸、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率的精确调节刺激反应药物传递系统。因此，拟议的研究计划侧重于开发先进的生物材料，用于制造细菌反应性ivr，这种ivr将提供抗生素封装纳米颗粒的可控持续递送，持续时间为10至14天。最初的重点将放在由新型聚氨酯复合生物材料合成的ivr的制造上，这种生物材料可以在特定细菌酶的存在下改变其组成。这些IVRs是为了应对女性生殖道微生物环境的变化而设计的，例如在正常生理条件下几乎没有药物释放，当外来细菌释放特定酶时药物释放迅速。将对新合成的生物材料进行物理化学表征，以确定其熔化温度、孔隙率、邵氏硬度等特性。这些不同性质对制备的IVRs结构特征的影响及其对抗生素包封纳米颗粒释放谱的影响也将被研究。将评估植入药物输送系统的生物相容性，其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功效。总的来说，拟议的研究计划是创新的，将显著促进材料科学领域的知识进步，通过产生新的细菌反应聚氨酯复合生物材料，以控制纳米颗粒的传递。最重要的是，在这个研究项目中训练的高素质人才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。

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.