Intraperitoneal administration of cabazitaxel-loaded nanoparticles in peritoneal metastasis models

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 encap-sulated 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. (c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/ by/4.0/).

Automated summary

Colorectal and ovarian cancers commonly spread to the peritoneum, for which treatment options are limited. This study investigated the use of nanoparticles to improve the intraperitoneal delivery of cabazitaxel taxane, leading to increased drug retention, longer residence time, and higher drug concentrations in peritoneal tumors. The encapsulation of cabazitaxel in nanoparticles improved the treatment response in in vivo models, suggesting its potential as a novel treatment for peritoneal metastases.