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.

腹部手术是许多疾病的重要治疗方法，但常见且严重的副作用。 腹部手术会形成术后粘连，术后粘连也会引起疼痛。 其他严重并发症，例如不孕症和肠梗阻，这些并发症影响许多患者。 因此，手术后粘连的治疗每年可能花费数十亿美元。 对开发可以预防术后粘连形成的策略和药物有浓厚的兴趣。 当前最小化粘附的策略通常涉及使用粘附减少液体和大量的粘附剂。 然而，临床研究表明，现有药物在减少粘连方面具有优势。 因此，迫切需要开发新的药物和策略来减少后遗症。 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。 仅在避免正常腹膜表面的同时避免组织损伤。纳米技术的最新进展使得这一技术成为可能。 开发可以靶向特定分子或组织（例如胶原蛋白）的纳米颗粒（NP）。 研究表明，我们可以利用这些纳米颗粒在手术损伤部位形成有针对性的微观屏障。 我们致力于优化我们的靶向纳米粒子和 2-NP 系统，以实现生物靶向屏障 我们进一步推测我们可以封装并提供抗炎治疗。 使用这些纳米粒子和这些含有纳米粒子的药物可以进一步降低术后粘连形成的风险。 该应用的中心目标是设计和优化生物靶向的可生物降解纳米粒子，这些纳米粒子可以结合 腹膜损伤部位，形成坚固的屏障并防止手术粘连。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，配制不同尺寸、成分、 结合化学物质并封装不同的抗炎治疗药物将被评估。 使用大鼠盆腔术后粘连模型预防粘连总之，我们的应用旨在。 应用纳米医学的进步来开发预防粘连的新型药物。 降低术后粘连风险的潜力，这将直接转化为患者的改善 生活质量。