Zosteric Acid Integrated Thermo-reversible Gels for Preventing Surgical Adhesions

用于预防手术粘连的 Zosteric Acid 集成热可逆凝胶

基本信息

批准号：
8232885
负责人：
Bi-min Newby
金额：
$ 37.64万
依托单位：
UNIVERSITY OF AKRON
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：
2012-06-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8232885
关键词：
Abdomen Acids Adhesions Adhesives Animals Anti-Adhesion Agent Area Behavior Binding Biological Factors Biomaterials Research Biomedical Research Cell Culture Techniques Cells Chemicals Cicatrix Clinical Clinical Trials Collaborations Collagen Communities Complex Complication Data Deposition Development Drug Compounding Drug Controls Drug Delivery Systems Effectiveness Encapsulated Engineering Ensure Expenditure Family suidae Fibrin Fibroblasts Film Funding Gel Glycolic-Lactic Acid Polyester Goals Grant Guidelines Health Health system Hospitalization Hour Human Human Activities Hydrogels Hydroxyl Radical In Vitro Infertility Inflammatory Institutes Journals Knowledge Laparoscopic Surgical Procedures Lead Learning Liquid substance Mammalian Oviducts Marines Mass Spectrum Analysis Medical Mentors Methods Methylcellulose Modeling Morbidity - disease rate Mus Nature Nuclear Magnetic Resonance Operative Surgical Procedures Organ Organism Pain Paper Patients Pelvis Pharmaceutical Preparations Phase Pluronics Prevention Production Property Proteins Publications Research Research Personnel Safety Science Scientist Site Solid Students Surface Surgical Management System Techniques Technology Time Tissue Engineering Tissues Toxic effect Training United States National Institutes of Health Universities Variant Water Work Zostera base biodegradable polymer career cell growth chemical synthesis clinical practice controlled release cytotoxicity design dosage drug synthesis graduate student high school in vivo insight meetings nanoparticle next generation pre-clinical prevent programs rhamnolipid scale up skills success symposium tissue culture

项目摘要

DESCRIPTION (provided by applicant): The development of adhesions following surgery represents a significant, costly morbidity typically expressed as pain and infertility in the patient. Availability of a reliable method to decrease occurrence of adhesions would constitute a beneficial advance in current surgical practice. However, the efficacy and utility in both open and laparoscopic surgery of currently approved standard adhesion barriers is limited. The goal of the proposed project is a delivery system that allows an initial burst of the anti-adhesion agent, zosteric acid (ZA), followed by a sustained release of the agent. Zosteric acid, a natural product extracted from eelgrass Zostera Marina, shows an extremely low toxicity but effectiveness in preventing adhesion formation of various organisms. It will be directly integrated, along with its nanoparticle-encapsulated form, into a thermo-reversible gel made of Pluronic(R) F-127 and Hydroxyl propyl methyl cellulose, which can then be easily applied in both open and laparoscopic surgeries to prevent adhesion development. The specific tasks include: (1) to successfully scale up the production of highly purified ZA; {(2) to assess the collagen deposition and fibroblast activities of human and mouse fibroblast cells using free form of ZA; (3)} to encapsulate ZA into micro/nanoparticles of a relatively rapid biodegradable polymer, poly(lactide-co-glycolide); (4) following encapsulation, we will first conduct in vitro culture studies to determine viability {of the thermo- reversible gel containing free form and micro/nanoparticle encapsulated ZA and} then in vivo studies. If cell culturing does not provide evidence of cell growth inhibition, we will repeat the encapsulation step utilizing an alternative drug (e.g. rhamnolipids) with the appropriate properties. When tissue culturing provides evidence of cell growth inhibition {and non-cytotoxic}, we will then determine the efficacy of the dual-delivery system in preventing adhesions in a swine model. While not to be included in this project, the next phase, following successful animal results, would be to pursue FDA approval and clinical trials. The proposed tasks have been designed to train and engage a team of a graduate, undergraduate and high school students. The involvement of undergraduate (via Tiered Mentoring) and high school students (via Project Lead the Way) are intended to promote and encourage careers in science, technology and engineering, an on-going effort that the PI has been actively participating in. The graduate student will not only be challenged to conduct research related to biomedicine, but also will be provided the opportunity to mentor underclassmen. Through informal discussion and weekly project meetings with the PIs, attending regional or national scientific meetings, and journal publications, the students trained in traditional chemical and material engineering will be given opportunities to explore the biomedical community. If funded, the proposed project would be one of the first NIH-funded researches in the Department of Chemical and Biomolecular Engineering at The University of Akron, a department on the rise in biomaterial research. PUBLIC HEALTH RELEVANCE: This AREA project is to develop a drug delivery system that allows an initial burst followed with a slow release of an anti-adhesive agent, zosteric acid, for the prevention of surgical adhesions. The Department of Chemical and Biomolecular Engineering at the University of Akron is developing focused research in the area of tissue engineering, drug delivery and biofouling based on an established research area, mainly contributed by PI, in biofouling/antifouling,. The program calls for a strong collaborative effort between our University and regional medical institutes, such as Summa Health System and NEOUCOM, and this AREA grant, if funded, will allow for such collaboration to expand and for the exposure of students to various health related research.

描述（由申请人提供）：手术后的粘连发展代表了一种显着的，昂贵的发病率，通常表示为患者的疼痛和不育。可靠的方法可用于减少粘连发生的可靠方法将构成当前手术实践中的有益进步。然而，当前批准的标准粘附障碍的开放和腹腔镜手术中的功效和效用都是有限的。提出的项目的目的是递送系统，该系统允许抗粘附剂，Zosteric酸（ZA）的初始爆发，然后持续释放代理。 Zosteric Acid是一种从鳗草Zostera码头中提取的天然产物，它表现出极低的毒性，但在防止形成各种生物的粘附形成方面的有效性。它将与纳米颗粒封装的形式直接整合到由pluronic（R）F-127和羟基丙基甲基纤维素制成的热可逆凝胶中，然后可以轻松地将其施加在开放式和腹腔镜手术中，以防止粘附发育。特定任务包括：（1）成功扩大高度纯化ZA的生产； {（2）使用ZA的自由形式评估人和小鼠成纤维细胞的胶原蛋白沉积和成纤维细胞活性；（3）}将ZA封装到相对快速的可生物降解聚合物聚合物（乳酸 - 糖糖苷）的微/纳米颗粒中；（4）封装后，我们将首先进行体外培养研究，以确定含有自由形式的热可逆凝胶和微粒子封装的ZA和}然后在体内研究。如果细胞培养不提供细胞生长抑制的证据，我们将使用具有适当特性的替代药物（例如鼠李糖脂）重复封装步骤。当组织培养提供细胞生长抑制的证据（和非胞毒性}}时，我们将确定双解传递系统在防止猪模型中粘附方面的疗效。虽然不纳入该项目，但成功的动物结果后，下一阶段将是进行FDA批准和临床试验。拟议的任务旨在培训和参与一个毕业生，本科和高中生的团队。本科（通过分层指导）和高中生（通过项目领导）的参与旨在促进和鼓励科学，技术和工程学的职业，这是PI积极参与的持续努力。研究生将不仅挑战与生物医学有关的研究，而且还将为教师提供与培训的机会。通过与PI的非正式讨论和每周的项目会议，参加区域或国家科学会议以及期刊出版物，接受了传统化学和材料工程培训的学生将有机会探索生物医学界。如果资助，该拟议的项目将是阿克伦大学化学和生物分子工程系的最早由NIH资助的研究之一，阿克伦大学是生物材料研究兴起的系。公共卫生相关性：该区域项目是开发一种药物输送系统，该系统允许初始爆发，然后缓慢释放抗粘附剂Zosteric Acide，以预防手术粘附。阿克伦大学的化学和生物分子工程系正在基于既定的研究领域，主要由PI贡献，在生物污染/抗污染领域，在组织工程，药物输送和生物污染领域开发重点研究。该计划要求我们的大学和区域医学机构（例如Summa Health System and Neoucom）进行强有力的合作，如果资助了该领域的赠款，将允许这种合作扩展并使学生接触各种与健康有关的研究。