Heparin interferes with the uptake of liposomes in glioma

Thomas S. van Solinge; Kristina Pagh Friis; Killian O'Brien; Romy L. Verschoor; Jeroen van Aarle; Arnold Koekman; Xandra O. Breakefield; Pieter Vader; Raymond Schiffelers; Marike Broekman

International Journal of Pharmaceutics: X (Dec 2023)

Heparin interferes with the uptake of liposomes in glioma

Thomas S. van Solinge,
Kristina Pagh Friis,
Killian O'Brien,
Romy L. Verschoor,
Jeroen van Aarle,
Arnold Koekman,
Xandra O. Breakefield,
Pieter Vader,
Raymond Schiffelers,
Marike Broekman

Affiliations

Thomas S. van Solinge: Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, MA 02114, USA; Department of Neurosurgery, Leiden University Medical Center, Leiden, the Netherlands; Corresponding author.
Kristina Pagh Friis: Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, MA 02114, USA
Killian O'Brien: Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, MA 02114, USA
Romy L. Verschoor: Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, MA 02114, USA
Jeroen van Aarle: Department of Neurosurgery, University Medical Center, Utrecht, the Netherlands
Arnold Koekman: Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, the Netherlands
Xandra O. Breakefield: Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, MA 02114, USA
Pieter Vader: CDL Research, University Medical Center Utrecht, Utrecht, the Netherlands
Raymond Schiffelers: Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, the Netherlands
Marike Broekman: Department of Neurology and Center for Molecular Imaging Research, Department of Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, MA 02114, USA; Department of Neurosurgery, Leiden University Medical Center, Leiden, the Netherlands; Department of Neurosurgery, Haaglanden Medical Center, The Hague, the Netherlands

Journal volume & issue: Vol. 6
p. 100191

Abstract

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In glioblastoma, a malignant primary brain tumor, liposomes have shown promise in pre-clinical and early phase clinical trials as delivery vehicles for therapeutics. However, external factors influencing cellular uptake of liposomes in glioma cells are poorly understood. Heparin and heparin analogues are commonly used in glioma patients to decrease the risk of thrombo-embolic events. Our results show that heparin inhibits pegylated liposome uptake by U87 glioma and GL261 cells in a dose dependent manner in vitro, and that heparin-mediated inhibition of uptake required presence of fetal bovine serum in the media. In a subcutaneous model of glioma, Cy5.5 labeled liposomes could be detected with in vivo imaging after direct intra-tumoral injection. Ex-vivo analysis with flow cytometry showed a decreased uptake of liposomes into tumor cells in mice treated systemically with heparin compared to those treated with vehicle only.

Published in International Journal of Pharmaceutics: X

ISSN: 2590-1567 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Pharmacy and materia medica
Website: https://www.journals.elsevier.com/international-journal-of-pharmaceutics-x

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