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

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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.

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Abbreviations

CRE:

CremophorEL

EPR:

Enhanced permeation and retention

HIPEC:

Hyperthermic intraperitoneal chemotherapy

IS:

Internal standard

LOQ:

Limit of quantitation

MALDI:

Matrix assisted laser desorption ionization

MP:

Mobile phase

MSI:

Mass spectrometry imaging

Nab :

Nanoparticles-albumin-bound

PTX:

Paclitaxel

ROI:

Region of interest

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ACKNOWLEDGMENTS AND DISCLOSURES

We acknowledge support to ED from Cariplo Foundation for the project (Project 2013–0692). The study was supported in part by funding from Celgene Corporation Grant-ITA-039 (M1266). The authors thank J.D. Baggott for editing the article.

Author information

Authors and Affiliations

  1. General, Emergency and Trauma Surgery Department Papa Giovanni XXIII hospital, Bergamo, Italy

    Federico Coccolini, Marco Ceresoli & Luca Ansaloni

  2. Dipartimento di Scienze Veterinarie per la Salute, la Produzione Animale e la Sicurezza Alimentare, Università degli Studi di Milano, Milan, Italy

    Fabio Acocella, Stefano Brizzola & Matteo Ghiringhelli

  3. Oncology Department, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy

    Lavinia Morosi, Maurizio D’Incalci & Massimo Zucchetti

  4. Mass Spectrometry Laboratory, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy

    Enrico Davoli

Authors
  1. Federico Coccolini
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  8. Luca Ansaloni
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  9. Maurizio D’Incalci
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  10. Massimo Zucchetti
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Corresponding author

Correspondence to Lavinia Morosi.

Ethics declarations

Procedures involving animals and their care were conducted in conformity with institutional guidelines that comply with national (DL26, March 2014) and international (EEC Council Directive 2010/63, August, 2013) laws and policies and in line with guidelines for the welfare and use of animals in cancer research.

Disclosure of Commercial Interest

None of the authors has any financial and personal relationships with other people or organizations to disclose, that could inappropriately influence their work.

Additional information

Federico Coccolini, Fabio Acocella and Lavinia Morosi equally contributed to this work

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Coccolini, F., Acocella, F., Morosi, L. et al. High Penetration of Paclitaxel in Abdominal Wall of Rabbits after Hyperthermic Intraperitoneal Administration of Nab-Paclitaxel Compared to Standard Paclitaxel Formulation. Pharm Res 34, 1180–1186 (2017). https://doi.org/10.1007/s11095-017-2132-4

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  • DOI: https://doi.org/10.1007/s11095-017-2132-4

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