Modelling the biophysical barriers to drug delivery in cancer

模拟癌症药物输送的生物物理障碍

• 批准号: 2881731
• 金额: --
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2881731
• 关键词: Modelling; biophysical; barriers; drug; delivery

Drugs that are injected into cardio-vasculature system the body in order to treat diseases such as cancer, encounter a number of biophysical barriers before ever reaching the diseased area. These include the endothelial barrier - the physical walls of the vasculature system, through which a drug must first pass effectively. Once beyond the vasculature system, the drugs encounter a mechanically rigid, oxygen depleted diseased matrix that can present another physical and chemical barrier to effective drug treatment. These biophysical barriers block and reduce the effectiveness of drug treatment, leading to treatment failure and disease re-occurrence. Yet their presence in the body, drug screening in the laboratory does not take into account these critical physical barriers leading to drugs that are effective in the lab, but fail once in clinic. This project will develop microfluidic, organ-on-chip technology to model the biophysical barriers encountered by chemotherapeutics in cancer treatment. In particular, devices will be designed and engineered to culture human microvasculature in order to unravel vasculature - drug interactions. In addition, these next-generation models will be used to investigate new therapeutics, such as microbubbles, as an alternative, improved route to drug delivery compared to conventional methods in treating cancer.

为了治疗诸如癌症的疾病而注射到身体的心血管系统中的药物在到达患病区域之前遇到许多生物物理障碍。这些包括内皮屏障-血管系统的物理壁，药物必须首先有效地通过。一旦超出脉管系统，药物遇到机械刚性的、氧耗尽的病变基质，其可以对有效的药物治疗呈现另一物理和化学屏障。这些生物物理屏障阻碍和降低药物治疗的有效性，导致治疗失败和疾病复发。然而，它们在体内的存在，实验室的药物筛选并没有考虑到这些关键的物理障碍，导致药物在实验室中有效，但在临床上一旦失败。该项目将开发微流体，器官芯片技术，以模拟癌症治疗中化疗药物遇到的生物物理障碍。特别地，将设计和工程化装置以培养人类微血管系统，以便解开血管系统-药物相互作用。此外，这些下一代模型将用于研究新的治疗方法，例如微泡，作为与治疗癌症的传统方法相比的替代、改进的药物递送途径。