In vitro assessment of nanomedicines' propensity to cause palmar-plantar erythrodysesthesia: A Doxil vs. doxorubicin case study

Author:

Cedrone,Edward

Ishaq, Abbas

Grabarnik, Emma

Edmondson,Elijah

Skoczen,Sarah

Neun,Barry

Freer, Matthew

Shuttleworth, Siannah

Sviland, Lisbet

Dickinson, Anne

Dobrovolskaia,Marina
Author Address

Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, 8560 Progress Drive, Frederick, MD 21701, USA., Alcyomics Ltd., Biosphere Draymans Way, Newcastle Helix, Newcastle upon Tyne NE4 5BX, United Kingdom., Molecular Histopathology Laboratory, Laboratory of Animal Sciences Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, 8560 Progress Drive, Frederick, MD 21701, USA., Department of Clinical Medicine, Faculty of Medicine, University of Bergen, Norway., Alcyomics Ltd., Biosphere Draymans Way, Newcastle Helix, Newcastle upon Tyne NE4 5BX, United Kingdom. Electronic address: anne.m.dickinson@alcyomics.com., Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, 8560 Progress Drive, Frederick, MD 21701, USA. Electronic address: marina@mail.nih.gov.,

Abstract:

Palmar-plantar erythrodysesthesia (PPE), also known as hand and foot syndrome, is a condition characterized by inflammation-mediated damage to the skin on the palms and soles of the hands and feet. PPE limits the successful therapeutic applications of anticancer drugs. However, identifying this toxicity during preclinical studies is challenging due to the lack of accurate in vitro and in vivo animal-based models. Therefore, there is a need for reliable models that would allow the detection of this toxicity early during the drug development process. Herein, we describe the use of an in vitro skin explant assay to assess traditional DXR, Doxil reference listed drug (RLD) and two generic PEGylated liposomal DXR formulations for their abilities to cause inflammation and skin damage. We demonstrate that the results obtained with the in vitro skin explant assay model for traditional DXR and Doxil correlate with the clinical data. Copyright © 2024. Published by Elsevier Inc.

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