结直肠癌和卵巢癌常常在腹腔形成转移，但治疗方法有限。腹腔内化疗表现出良好的治疗效果，但药物的快速清除和全身毒性是限制其应用的因素。因此，我们将卡班肝素納米粒子（NP）包覆在聚（烷基氰基丙酸酯）（PACA）中，旨在改善腹腔内给药量。通过监测临床表现、器官重量和血液造血和生化参数，在大鼠中研究了游离和包埋卡班肝素的毒性。在小鼠中评估了药代动力学、生物分布和治疗反应。通过测量卡班肝素和2-乙基丁醇NP降解产物，研究了生物分布。结果显示，药物包埋可提高腹腔内药物滞留，延长腹腔内药物滞留时间，并在腹腔肿瘤中提高药物浓度。因此，卡班肝素的包埋改善了内腔肿瘤模型的治疗反应。总之，这些观察表明，基于NP的卡班肝素包埋具有治疗腹腔转移的强大潜力。版权所有© 2023 Elsevier Inc.，由作者出版。保留所有权利。

Colorectal and ovarian cancers frequently develop peritoneal metastases with few treatment options. Intraperitoneal chemotherapy has shown promising therapeutic effects, but is limited by rapid drug clearance and systemic toxicity. We therefore encapsulated the cabazitaxel taxane in poly(alkyl cyanoacrylate) (PACA) nanoparticles (NPs), designed to improve intraperitoneal delivery. Toxicity of free and encapsulated cabazitaxel was investigated in rats by monitoring clinical signs, organ weight and blood hematological and biochemical parameters. Pharmacokinetics, biodistribution and treatment response were evaluated in mice. Biodistribution was investigated by measuring both cabazitaxel and the 2-ethylbutanol NP degradation product. Drug encapsulation was shown to increase intraperitoneal drug retention, leading to prolonged intraperitoneal drug residence time and higher drug concentrations in peritoneal tumors. As a result, encapsulation of cabazitaxel improved the treatment response in two in vivo models bearing intraperitoneal tumors. Together, these observations indicate a strong therapeutic potential of NP-based cabazitaxel encapsulation as a novel treatment for peritoneal metastases.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.