Intraperitoneal administration of cabazitaxel-loaded nanoparticles in peritoneal metastasis models

What you’ll learn in this article:

PACA drug encapsulation improves treatment response in peritoneal metastases models.
Intraperitoneal injection of PACA nanoparticles provides a beneficial drug biodistribution.
Drug encapsulation in PACA nanoparticles improves intraperitoneal drug retention.
The taxane cabazitaxel is a promising chemotherapy option for peritoneal metastases.

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.

Graphical Abstract:

February 27, 2023