Kellogg College, University of Oxford, Oxford, UK.
Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Expert Opin Drug Deliv. 2022 Aug;19(8):899-912. doi: 10.1080/17425247.2022.2099834. Epub 2022 Jul 21.
Many small molecules and biologic therapeutics have been developed for solid tumor therapy. However, the unique physiology of tumors makes the actual delivery of these drugs into the tumor mass inefficient. Such delivery requires transport from blood vessels, across the vasculature and into and through interstitial space within a tumor. This transportation is dependent on the physiochemical properties of the therapeutic agent and the biological properties of the tumor. It was hoped the application of nanoscale drug carrier systems would solve this problem. However, issues with poor tumor accumulation and limited drug release have impeded clinical impact. In response, these carrier systems have been redesigned to be paired with targetable external mechanical stimuli which can trigger much enhanced drug release and deposition.
The pre-clinical and clinical progress of thermolabile drug carrier systems and the modalities used to trigger the release of their cargo are assessed.
Combined application of mild hyperthermia and heat-responsive liposomal drug carriers has great potential utility. Clinical trials continue to progress this approach and serve to refine the technologies, dosing regimens and exposure parameters that will provide optimal patient benefit.
许多小分子和生物治疗药物已被开发用于实体瘤治疗。然而，肿瘤的独特生理学使得这些药物实际进入肿瘤块的效率低下。这种输送需要从血管中运输，穿过血管，进入并穿过肿瘤内的间质空间。这种运输取决于治疗剂的物理化学性质和肿瘤的生物学特性。人们希望纳米级药物载体系统的应用能够解决这个问题。然而，肿瘤积累不良和药物释放有限的问题阻碍了其临床应用。作为回应，这些载体系统被重新设计为与可靶向的外部机械刺激配对，这可以触发药物的释放和沉积。
评估了热敏药物载体系统的临床前和临床进展以及用于触发其货物释放的方式。
温和的热疗和热响应脂质体药物载体的联合应用具有很大的潜在应用价值。临床试验继续推进这一方法，并有助于完善技术、剂量方案和暴露参数，从而为患者提供最佳获益。
