Basement Membrane Targeted Nanoparticles for Post-Surgical Adhesion Prevention

腹部手术是许多疾病的重要治疗方法。一种频繁而严重的副作用 腹部手术是手术后形成的粘连。手术后粘连会导致疼痛以及 不孕不育、肠梗阻等其他严重并发症。这些并发症影响了许多患者。 而手术后粘连的管理每年可能要花费数十亿美元。因此，一直以来， 对开发可防止术后粘连形成的策略和试剂有浓厚兴趣。 目前最大限度减少粘连的策略通常包括使用减粘液和大剂量 身体上的障碍。然而，临床研究表明，现有药物在减少粘连方面的好处 是相当有限的。因此，迫切需要开发新的代理人和战略，以减少后遗症。 外科粘连。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 只有在避免正常腹膜表面的情况下，才能防止组织损伤。纳米技术的最新进展使 针对特定分子或组织的纳米粒子(NPs)的开发，如胶原蛋白。我们有 结果表明，我们可以利用这些纳米颗粒在手术损伤部位形成靶向微观屏障。我们 假设我们优化我们的靶向NP和2-NP系统，以实现生物靶向屏障 防止粘连。我们进一步推论，我们可以封装和输送抗炎治疗药物 使用这些NPs和这些含有药物的NPs可以进一步降低手术后粘连形成的风险。这个 这项应用的中心目标是设计和优化生物靶向的可生物降解的NPs，该NPs可以结合 对于腹膜损伤部位，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目标NP平台，制定不同大小、组成、 结合化学，并封装不同的抗炎治疗药物。将对这些核动力源进行评估 用大鼠盆腔手术后粘连模型预防粘连。总之，我们的应用程序旨在 应用纳米医学的进展，开发新型粘连防粘剂。我们提议的工作有 有可能降低术后粘连的风险，这将直接转化为患者的 生活质量。

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.