High Penetration of Paclitaxel in Abdominal Wall of Rabbits after Hyperthermic Intraperitoneal Administration of Nab-Paclitaxel Compared to Standard Paclitaxel Formulation

Federico Coccolini, Fabio Acocella, Lavinia Morosi, Stefano Brizzola, Matteo Ghiringhelli, Marco Ceresoli, Enrico Davoli, Luca Ansaloni, Maurizio D’Incalci, Massimo Zucchetti

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Paclitaxel (PTX) is currently used in combination with cisplatin for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis. Albumin-bound PTX is a promising new drug for HIPEC because of its easy solubility in aqueous perfusion medium and possibly because of the tendency of albumin to cross physiological barriers and accumulate in tumor tissue. Methods: We tested the feasibility of using nab-paclitaxel in rabbits treated by HIPEC for 60 min compared with the classical formulation at an equivalent PTX dose. Samples of perfusate and blood were collected at different time points and peritoneal tissues were collected at the end of perfusion. PTX concentrations were determined by HPLC. The depth of paclitaxel penetration through the peritoneal barrier was assessed by mass spectrometry imaging. Results: PTX after nab-paclitaxel treatment penetrated up to 0.63 mm in the peritoneal wall, but after CRE-paclitaxel, it was not detectable in the peritoneum. Moreover, the peritoneal concentration after nab-paclitaxel was five times that after paclitaxel classical formulation. Despite the high levels reached in the peritoneum, systemic exposure of PTX was low. Conclusions: Our results show that nab-paclitaxel penetrates into the abdominal wall better than CRE-paclitaxel, in terms of effective penetration and peritoneal tissue concentration.

Original languageEnglish
Pages (from-to)1180-1186
Number of pages7
JournalPharmaceutical Research
Volume34
Issue number6
DOIs
Publication statusPublished - Jun 1 2017

Keywords

  • intraperitoneal chemoterapy
  • mass spectrometry imaging
  • nab-paclitaxel
  • nanoparticles
  • peritoneal carcinomatosis

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'High Penetration of Paclitaxel in Abdominal Wall of Rabbits after Hyperthermic Intraperitoneal Administration of Nab-Paclitaxel Compared to Standard Paclitaxel Formulation'. Together they form a unique fingerprint.

Cite this