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Intraperitoneal administration of cabazitaxel-loaded nanoparticles in peritoneal metastasis models

Abstract

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.
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Category

Academic article

Language

English

Author(s)

Affiliation

  • SINTEF Industry / Biotechnology and Nanomedicine
  • University of Oslo
  • St. Olavs Hospital, Trondheim University Hospital
  • Norwegian University of Science and Technology
  • Oslo University Hospital

Year

2023

Published in

Nanomedicine: Nanotechnology, Biology and Medicine

ISSN

1549-9634

Volume

48

Page(s)

1 - 11

View this publication at Norwegian Research Information Repository