Intraperitoneal administration of cabazitaxel-loaded nanoparticles in peritoneal metastasis models

Astrid Hyldbakk; Karianne Giller Fleten; Sofie Snipstad; Andreas K O Åslund; Catharina de Lange Davies; Kjersti Flatmark; Yrr Mørch

doi:10.1016/j.nano.2023.102656

Intraperitoneal administration of cabazitaxel-loaded nanoparticles in peritoneal metastasis models

Nanomedicine. 2023 Feb:48:102656. doi: 10.1016/j.nano.2023.102656. Epub 2023 Jan 14.

Authors

Astrid Hyldbakk¹, Karianne Giller Fleten², Sofie Snipstad³, Andreas K O Åslund⁴, Catharina de Lange Davies⁵, Kjersti Flatmark⁶, Yrr Mørch⁷

Affiliations

¹ Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway; Department of Physics, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. Electronic address: astrid.hyldbakk@sintef.no.
² Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: karianne.giller.fleten@rr-research.no.
³ Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway; Department of Physics, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Cancer Clinic, St. Olav's Hospital, Trondheim, Norway. Electronic address: sofie.snipstad@sintef.no.
⁴ Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway. Electronic address: andreas.aaslund@sintef.no.
⁵ Department of Physics, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. Electronic address: catharina.davies@ntnu.no.
⁶ Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. Electronic address: kjersti.flatmark@rr-research.no.
⁷ Department of Biotechnology and Nanomedicine, SINTEF Industry, Trondheim, Norway. Electronic address: yrr.morch@nadeno.com.

PMID: 36646195
DOI: 10.1016/j.nano.2023.102656

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.

Keywords: Cabazitaxel; Drug delivery; Intraperitoneal administration; Peritoneal metastases; Poly(alkyl cyanoacrylate) nanoparticles.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Mice
Nanoparticles*
Peritoneal Neoplasms* / drug therapy
Rats
Taxoids / pharmacology
Taxoids / therapeutic use
Tissue Distribution

Substances

cabazitaxel
Taxoids