Engineering Tissue Level Targeting of Biologic Drugs via Automated Interfacial Microneedle Pumps

项目摘要/摘要： 生物药物已经改变了各种疾病的治疗方法，包括糖尿病、癌症和心脏病 疾病。然而，它们的巨大体积阻止了它们在给药时很容易扩散到靶组织。 口服或皮下注射。例如，胃肠粘膜组织、心肌组织和 实体肿瘤组织密密麻麻，大分子几乎无法穿透数百微米。 从植入的药库或泄漏的血管进入组织。这可以防止药物，如细胞因子， 已经被证明可以促进心肌梗死模型的伤口愈合，从到达 受影响的组织区域，它们可以提供治疗效果。即使当地的药品管理局 越来越有必要提供治疗效果，但目前还没有研究或工具来了解 液体流入组织的过程。取而代之的是，医疗专业人员以不同的流速手动注射药物，并 压力，导致不一致的护理和潜在的破坏性后果。输送的毒品也太多了 可以迅速清除实体肿瘤中的癌细胞，促进它们的循环和产生额外的 转移瘤。它还可能导致药物从实体肿瘤中泄漏出来，产生全身摄取和偏离靶点。 效果。另一方面，交付速度太慢可能会产生仓库配置文件，其中 药物和受影响组织的长度大于药物容易扩散的长度。这项提案将把重点放在 浅谈医护人员标准化、自动化注射系统的开发 组织注射。以与组织的机械和生理特性相适应的最佳流量注射 将允许更大的药物分布，同时防止产生的非靶向副作用和组织损伤 由强力注射引起。这一建议的成功将产生(1)能够预测的计算模型 不同注射特性下药物在心脏和实体肿瘤组织中的分布以及(2)临床 可翻译注射系统，优化和标准化伤口愈合药物和 分别对这些组织进行免疫治疗。

Project Summary/Abstract: Biologic drugs have transformed the treatments of a variety of diseases, including diabetes, cancer, and heart disease. However, their large size prevents them from easily diffusing into targeted tissues when administered orally or via subcutaneous injection. For example, gastrointestinal mucosal tissue, myocardial muscle tissue and solid tumor tissue are so densely packed that macromolecules can barely penetrate hundreds of micrometers into the tissue from an implanted drug depot or leaky blood vessel. This prevents drugs, such as cytokines that have been demonstrated to promote wound healing in models of myocardial infarction, from reaching the impacted tissue areas where they could provide therapeutic effects. Even though local administration of drugs is becoming increasingly necessary to provide therapeutic efficacy, no research or tools exist on understanding the flow of fluid into tissue. Instead, healthcare professionals inject drugs manually with varying flow rates and pressures, leading to inconsistent care and potentially devastating consequences. Delivering too much drug too quickly may dislodge cancer cells in a solid tumor, promoting their circulation and generation of additional metastases. It may also cause drug to leak out of the solid tumor, generating systemic uptake and off-target effects. Delivering too slowly, on the other hand, may generate a depot profile where the distance between the drug and the impacted tissue is greater than the length that the drug can readily diffuse. This proposal will focus on developing an injection system for healthcare professionals to perform standardized and automated internal tissue injections. Injecting at flow rates optimized to the mechanical and physiological properties of the tissue will allow for greater drug distributions while preventing the off-target side effects and tissue damage generated from overpowered injections. Success of this proposal will yield (1) a computational model capable of predicting drug distributions in heart and solid tumor tissue at various injection characteristics as well as (2) a clinically translatable injection system that optimizes and standardizes injections of wound healing drugs and immunotherapies into these tissues, respectively.