Engineering Bacteria-Responsive Intravaginal Rings for Controlled Drug Delivery

植入物的主要优势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传递药物。这种制造方法导致了一种基于基质的系统，该系统只允许小分子药物从聚合物中扩散。根据目前的设计，不可能从植入系统输送核酸、蛋白质/多肽或纳米载体系统。材料科学领域的一个主要挑战是开发能够产生可预测的药物释放速率的精确调节的刺激响应型药物输送系统。因此，拟议的研究计划集中在开发先进的生物材料，用于制造细菌响应性静脉注射受体，这种材料将提供可控的持续输送抗生素包裹的纳米颗粒14天。最初的重点将是制造由新型聚氨酯复合生物材料合成的静脉内注射受体，这种材料在特定细菌酶存在的情况下改变其组成。这些IVR的设计是为了对女性生殖道微生物区系环境的变化做出反应，例如，在正常生理条件下很少甚至没有药物释放，以及当外来细菌释放特定的酶时，药物快速释放。将对新合成的生物材料进行物理化学表征，以确定熔化温度、孔隙率、肖氏硬度等性质。这些不同性质对制备的IVR的结构特征的影响以及对抗生素纳米粒释放的影响也将被研究。植入给药系统将进行生物兼容性、在特定细菌存在的情况下释放药物的能力、长期稳定性和减少细菌生长的有效性的评估。总体而言，拟议的研究计划是创新的，将通过产生新型细菌响应性聚氨酯复合生物材料来控制纳米颗粒的输送，从而极大地促进材料科学领域知识的进步。最重要的是，经过这一研究项目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。

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.