Department of GI Surgery, Ghent University Hospital, Ghent, Belgium.
Cancer Research Institute Ghent (CRIG), Belgium.
Expert Opin Drug Deliv. 2020 Apr;17(4):511-522. doi: 10.1080/17425247.2020.1736551. Epub 2020 Mar 18.
: The rationale for intraperitoneal (IP) drug delivery for patients with peritoneal metastases (PM) is based on the pharmacokinetic advantage resulting from the peritoneal-plasma barrier, and on the potential to adequately treat small, poorly vascularized PM. Despite a history of more than three decades, many aspects of IP drug delivery remain poorly studied.: We outline the anatomy and physiology of the peritoneal cavity, including the pharmacokinetics of IP drug delivery. We discuss transport mechanisms governing tissue penetration of IP chemotherapy, and how these are affected by the biomechanical properties of the tumor stroma. We provide an overview of the current clinical evidence on IP chemotherapy in ovarian, colorectal, and gastric cancer. We discuss the current limitations of IP drug delivery and propose several potential areas of progress.: The potential of IP drug delivery is hampered by off-label use of drugs developed for systemic therapy. The efficacy of IP chemotherapy for PM depends on cancer type, disease extent, and mode of drug delivery. Results from ongoing randomized trials will allow to better delineate the potential of IP chemotherapy. Promising approaches include IP aerosol therapy, prolonged delivery platforms such as gels or biomaterials, and the use of nanomedicine.
: 腹腔内(IP)给药治疗腹膜转移(PM)患者的基本原理基于腹膜-血浆屏障带来的药代动力学优势,以及对治疗体积小、血供差的 PM 的潜在能力。尽管有三十多年的历史,但 IP 药物输送的许多方面仍研究不足。
: 我们概述了腹腔的解剖和生理学,包括 IP 药物输送的药代动力学。我们讨论了影响 IP 化疗药物向组织穿透的转运机制,以及肿瘤基质的生物力学特性如何影响这些机制。我们概述了目前在卵巢癌、结直肠癌和胃癌中应用 IP 化疗的临床证据。我们讨论了当前 IP 药物输送的局限性,并提出了几个潜在的进展领域。
: IP 药物输送的潜力受到为全身治疗开发的药物的标签外使用的阻碍。PM 的 IP 化疗疗效取决于癌症类型、疾病程度和药物输送方式。正在进行的随机试验的结果将有助于更好地描绘 IP 化疗的潜力。有前途的方法包括 IP 气溶胶治疗、延长释放的平台(如凝胶或生物材料),以及纳米医学的应用。