a Laboratory for Experimental Surgery, Department of Surgery , Ghent University , Ghent , Belgium.
b Department of Radiation Oncology and Experimental Cancer Research , Ghent University , Ghent , Belgium.
Int J Hyperthermia. 2017 Aug;33(5):534-542. doi: 10.1080/02656736.2017.1312563.
Intraperitoneal (IP) drug delivery, either as an intraoperative chemoperfusion or as an adjuvant, repeated instillation, is an established treatment modality in patients with peritoneal carcinomatosis. The efficacy of IP drugs depends on its ability to penetrate the tumour stroma in order to reach their (sub)cellular target. It is known, that drug penetration after IP delivery is limited to a few millimetres. Here, we review the basic tissue transport mechanisms after IP delivery and discuss the biophysical barriers and obstacles that limit penetration distance. In addition, we review the physical and pharmaceutical interventions that have been studied in order to improve delivery of small molecular and macromolecular drugs after IP instillation. These interventions could inform the design of future clinical trials aiming at an improved efficacy of IP-based drug delivery in carcinomatosis patients.
腹腔内(IP)药物输送,无论是作为术中化疗灌注还是辅助、重复灌注,都是腹膜癌病患者的一种既定治疗方式。IP 药物的疗效取决于其穿透肿瘤基质以达到(亚)细胞靶标的能力。众所周知,IP 给药后药物的穿透深度仅限于几毫米。在这里,我们回顾了 IP 给药后的基本组织转运机制,并讨论了限制穿透距离的生物物理屏障和障碍。此外,我们还回顾了为改善 IP 灌注后小分子和大分子药物输送而研究的物理和药物干预措施。这些干预措施可以为旨在提高癌病患者基于 IP 的药物输送疗效的未来临床试验提供信息。