Basement Membrane Targeted Nanoparticles for Post-Surgical Adhesion Prevention

用于预防术后粘连的基底膜靶向纳米颗粒

• 批准号: 10538489
• 负责人: Andrew Zhuang Wang
• 金额: $ 15.95万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10538489
• 关键词: Basement; Membrane; Targeted; Nanoparticles; Post

Abdominal surgery is an important treatment for many diseases. A frequent and serious side effect of abdominal surgery is the formation of post-surgical adhesions. Post-surgical adhesions can cause pain as well as other serious complications such as infertility and bowel obstruction. These complications affect many patients and the management of post-surgical adhesions can costs billions of dollars each year. Therefore, there has been strong interest in the development of strategies and agents that can prevent post-surgical adhesion formation. Current strategies to minimize adhesions generally involve the use of adhesion reducing liquids and large physical barriers. However, clinical studies have shown that the benefits of existing agents in reducing adhesions are quite limited. Thus, there is a strong need for the development of novel agents and strategies to reduce post- surgical adhesions. A key challenge in this effort is to provide barrier function and reduce inflammation at sites of tissue injury only while avoiding normal peritoneal surfaces. Recent advances in nanotechnology have enabled the development of nanoparticles (NPs) that can target specific molecules or tissue, such as collagen. We have shown that we can utilize these nanoparticles to form targeted microscopic barriers at sites of surgical injury. We hypothesize that we optimize our targeted NPs and the 2-NP system to enable a biologically targeted barrier for adhesion prevention. We further theorize that we can encapsulate and deliver anti-inflammatory therapeutics using these NPs and these drug containing NPs can further reduce risk of post-surgical adhesion formation. The central goal of this application is to engineer and optimize biologically targeted biodegradable NPs that can bind to sites of peritoneal injury, form a robust barrier and prevent surgical adhesion. To accomplish this goal, we plan to utilize our existing BM-targeted NP platform and formulate NPs with different sizes, compositions, binding chemistries, and encapsulate different anti-inflammatory therapeutics. These NPs will be evaluated for adhesion prevention using rat models of pelvic post-surgical adhesion. In summary, our application aims to apply advances in nanomedicine to develop novel agents for adhesion prevention. Our proposed work has potential to reduce the risk of post-surgical adhesion which will directly translate into improvement in patients’ quality of life.

腹部手术是治疗多种疾病的重要手段。一种常见的严重副作用， 腹部手术是术后粘连的形成。术后粘连可引起疼痛， 其他严重并发症，如不孕症和肠梗阻。这些并发症影响许多患者 并且术后粘连的处理每年花费数十亿美元。因此出现 对预防术后粘连形成的策略和药物的开发有浓厚的兴趣。 目前最小化粘连的策略通常涉及使用降低粘连的液体和大分子聚合物。 物理屏障。然而，临床研究表明，现有药物在减少粘连方面的益处 是相当有限的。因此，迫切需要开发新的药物和策略来减少后- 手术粘连这项工作的一个关键挑战是提供屏障功能并减少部位的炎症 避免正常腹膜表面的情况下组织损伤。纳米技术的最新进展使 纳米颗粒（NP）的发展，可以针对特定的分子或组织，如胶原蛋白。我们有 表明我们可以利用这些纳米粒子在手术损伤部位形成靶向的微观屏障。我们 假设我们优化了我们的靶向NP和2-NP系统，以实现生物靶向屏障， 防粘连我们进一步理论化，我们可以封装和提供抗炎治疗， 使用这些NP和这些含药NP可进一步降低术后粘连形成的风险。的 本申请的中心目标是设计和优化生物靶向的可生物降解的NP，其可以结合 腹膜损伤部位，形成坚固的屏障，防止手术粘连。为了实现这一目标，我们 计划利用我们现有的BM靶向NP平台，配制具有不同大小，组成， 结合化学物质，并封装不同的抗炎治疗剂。将对这些NP进行评价， 使用盆腔手术后粘连的大鼠模型预防粘连。总之，我们的申请旨在 应用纳米医学的进步来开发新的防粘连剂。我们提出的工作 降低术后粘连风险的可能性，这将直接转化为患者生活质量的改善 生活质量