Cyclodextrin-based Microparticle Polymer Formulations for the Slow and Sustained

描述(申请人提供)：医疗器械失效的主要原因之一是感染。尤其是腹股沟修补术后的人工网片感染是一个常见的外科问题，没有理想的解决方案，通常需要通过昂贵的病态干预进行植入物切除。预防短期和长期网状感染的选择是次优的。这种情况需要一个紧急的解决方案，因为修复体在疝气手术中被普遍使用。我们的长期目标是提供一种基于亲和力的微粒制剂，能够通过局部输送治疗水平的抗生素来预防或治疗疝气感染。这项建议的目标是开发一种基于亲和力的微粒配方，并证明它的效果与之前在凯斯西储大学开发的疝气网状涂层相当，后者能够预防网状感染，但作为设备涂层面临着复杂的转化途径。这项研究中产生的基于亲和力的微粒制剂将在感染的慢性疝修补术模型中长期预防和治疗网状败血症。中心假设是，持续、长期的局部；从微粒制剂中输送抗生素可以有效地治疗和根除与涂层网片相媲美的腹股沟网片部位感染所涉及的常见细菌病原体。这项工作将完成三个目标：1)制备基于亲和力的抗生素缓释微粒，并对其进行物理和化学表征；2)通过治疗细菌草坪和评估治疗效果，验证缓释平台的体外杀菌效果；3)通过检测聚合物涂层假体对疝修补体耐久性的影响，以及评估微粒子长期(30天)释放抗生素的治疗水平，展示体内治疗和预防装置感染的效果。我们提议的工作是创新的；它使用局部的、持续的方法来实现无感染的假体。预期的结果包括一种比设备涂层具有更现实的转换可能性的产品，即作为一个独立的平台。这些结果将对普通外科领域产生积极影响，因为它为自近50年前网状物问世以来一直使外科护理复杂化的棘手问题提供了解决方案。第二阶段的未来工作将把这些概念转化为其他手术装置、手术部位感染和一般伤口敷料。

DESCRIPTION (provided by applicant): One of the leading causes of failure for medical devices is infection. In particular synthetic mesh infections after ventral hernia repair are a common surgical problem with no ideal solution often requiring implant excision through costly morbid interventions. Options to prevent short and long term mesh infections are suboptimal. This situation calls for an urgent solution as prosthetics are universally used in hernia surgery. Our long-term goal is to provide an affinity-based microparticle formulation capable of preventing or treating hernia mesh infections by locally delivering therapeutic levels of antibiotics. The objective of this proposal is to develop an affinity-based microparticle formulation and demonstrate that it is comparable in effect to previously investigated hernia mesh coatings developed at Case Western Reserve University, which were able to prevent mesh infections but faced a complicated translation pathway as a device coating. The affinity-based microparticle formulations generated in this study will be evaluated in the long- term prevention and treatment of mesh sepsis in an infected chronic hernia repair model. The central hypothesis is that sustained, long-term local; delivery of antibiotics from a microparticle formulation can effectively treat and eradicate common bacterial pathogens involved in hernia mesh site infections comparable to that of a coated mesh. This work will be accomplished in three aims:1) Produce affinity- based antibiotic delivery microparticles and characterize them both physically and chemically; 2) Validate the microbicidal effect of delivery platform in vitro by treating bacterial lawns and evaluating therapeutic efficacy; and 3) Demonstrate that treatment and prevention of device infection in vivo by examining effects of polymer coated prosthetics on durability of hernia repair, and evaluating long-term (30-day) release of therapeutic levels of antibiotics from the microparticles. Our proposed work is innovative; it uses a local, sustained approach to achieve an infection-free prosthetic. The expected outcomes include a product which has a more realistic translation likelihood than device coatings, namely as a stand-alone platform. These results will positively impact the field of general surgery by providing a solution to a vexing problem that has complicated surgical care since meshes were introduced nearly 50 years ago. Future work in Phase II will translate these concepts into other surgically placed devices, surgical site infections, and wound dressings in general.