Cyclodextrin-based Microparticle Polymer Formulations for the Slow and Sustained

描述（由申请人提供）：医疗器械失效的主要原因之一是感染。特别是腹疝修补后的合成补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手术切除植入物。防止短期和长期网状物感染的选择都不是最理想的。这种情况迫切需要解决，因为修复术在疝气手术中普遍使用。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补片感染。该提案的目的是开发一种基于亲和力的微粒配方，并证明其效果与凯斯西储大学开发的先前研究的疝网涂层相当，后者能够防止网片感染，但作为设备涂层面临复杂的转化途径。本研究中产生的基于亲和力的微粒制剂将在感染慢性疝修补模型中长期预防和治疗网状败血症中进行评估。中心假设是持续的，长期的局部；从微粒制剂中递送抗生素可以有效地治疗和根除疝网部位感染中涉及的常见细菌病原体，与涂层网片相当。这项工作将在三个方面完成：1)生产基于亲和力的抗生素递送微粒，并对其进行物理和化学表征；2)通过处理细菌草坪，评价治疗效果，验证输送平台的体外杀微生物效果；3)通过检测聚合物包被修复体对疝气修复耐久性的影响，以及评估微颗粒中抗生素治疗水平的长期（30天）释放，证明在体内治疗和预防器械感染。我们提出的工作是创新的；它使用局部、持续的方法来实现无感染的假肢。预期的结果包括一个比设备涂层具有更现实的翻译可能性的产品，即作为一个独立的平台。这些结果将对普外科领域产生积极的影响，因为它为一个令人烦恼的问题提供了解决方案，这个问题自近50年前引入网格以来一直使外科护理复杂化。第二阶段的未来工作将把这些概念转化为其他手术放置设备、手术部位感染和伤口敷料。

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.