Cyclodextrin-based Microparticle Polymer Formulations for the Slow and Sustained

用于缓慢和持续的环糊精基微粒聚合物配方

基本信息

批准号：
8250887
负责人：
Julius N. Korley
金额：
$ 20万
依托单位：
AFFINITY THERAPEUTICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8250887
关键词：
Abdomen Activities of Daily Living Affinity Animal Model Animal Testing Animals Antibiotics Bacteria Binding Biological Assay Caring Characteristics Chronic Clinical Contracts Cyclodextrins Data Defect Devices Diffusion Drug Delivery Systems Drug Formulations Drug Kinetics Excision Flushing Future Goals Healthcare Systems Hernia Implant In Vitro Incidence Infection Infection prevention Infectious Agent Injury Intervention Intestines Laparotomy Lead Licensing Life Marketing Measures Medical Device Medical Device Failures Modeling Obesity Operative Surgical Procedures Outcome Pathway interactions Patients Pharmaceutical Preparations Phase Polymers Positioning Attribute Prevention Procedures Production Prosthesis Public Health Rifampin Sepsis Site Skin Small Business Innovation Research Grant Solutions Sterile coverings Sterility Technology Testing Therapeutic Therapeutic Uses Time Tissues Translating Translations Treatment Efficacy United States Universities Validation Ventral Hernia Work Wound Infection aging population bactericide base commercial application controlled release cost implantable device implantation in vivo innovation killings microbicide mouse model particle pathogen phase 1 study prevent repaired scale up standard of care success therapeutic effectiveness wound

项目摘要

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. PUBLIC HEALTH RELEVANCE: This proposal is critically concerned with the issue of public health in that its 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 short-term goals are to generate a stand-alone microparticle formulation that will be used to concurrently with hernia repair meshes at the time of implantation and then load them with therapeutic antibiotics to treat the most prevalent infectious organisms, without impacting the capacity of that mesh to adequately perform as a durable hernia repair prosthetic. We will assess the efficacy of delivery using a chronic infection mouse model developed at Case Western Reserve University.

描述（由申请人提供）：医疗器械失效的主要原因之一是感染。特别是腹疝修复后的合成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措施切除植入物。预防短期和长期网状感染的选项并不理想。由于疝气手术普遍使用假肢，这种情况需要紧急解决。我们的长期目标是提供一种基于亲和力的微粒制剂，能够通过局部递送治疗水平的抗生素来预防或治疗疝网感染。该提案的目的是开发一种基于亲和力的微粒制剂，并证明其效果与之前研究的凯斯西储大学开发的疝气网涂层相当，后者能够预防网状感染，但面临着复杂的翻译途径，因为器件涂层。本研究中产生的基于亲和力的微粒制剂将在感染的慢性疝气修复模型中的网状败血症的长期预防和治疗中进行评估。中心假设是持续的、长期的局部；与涂层网片相比，微粒制剂输送抗生素可以有效治疗和根除与疝气网片部位感染有关的常见细菌病原体。这项工作将实现三个目标：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）通过处理菌苔并评价疗效，验证递送平台的体外杀菌效果； 3) 通过检查聚合物涂层假体对疝气修复持久性的影响，并评估微粒中抗生素治疗水平的长期（30 天）释放，证明体内装置感染的治疗和预防。我们提出的工作是创新的；它采用局部、持续的方法来实现无感染的假肢。预期的结果包括一种比设备涂层具有更现实的转化可能性的产品，即作为一个独立的平台。这些结果将为普通外科领域带来积极影响，为自近 50 年前引入网格以来使外科护理变得复杂的棘手问题提供解决方案。第二阶段的未来工作将把这些概念转化为其他手术放置的设备、手术部位感染和一般伤口敷料。公共健康相关性：该提案与公共健康问题密切相关，因为其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网感染。短期目标是产生一种独立的微粒制剂，在植入时与疝气修复网同时使用，然后在其中装载治疗性抗生素来治疗最流行的感染性生物体，而不影响其能力网片足以作为耐用的疝气修复假体。我们将使用凯斯西储大学开发的慢性感染小鼠模型来评估递送效果。