Liposomal Irinotecan for Treatment of Colorectal Cancer in a Preclinical Model

Cancers
Jiao-Ren HuangHan-Chun Wu

Abstract

Colorectal cancer (CRC) is the most frequently diagnosed cancer and leading cause of cancer-related deaths worldwide. Because of the use of first-line CRC treatments, such as irinotecan (IRI), is hindered by dose-limiting side effects, improved drug delivery systems may have major clinical benefits for CRC treatment. In this study, we generate and characterize liposomal irinotecan (Lipo-IRI), a lipid-based nanoparticle, which shows excellent bioavailability and pharmacokinetics. Additionally, this formulation allows IRI to be maintained in active form and prolongs its half-life in circulation compared to IRI in solution. Compared with IRI statistically, the level of prostaglandin E2 (PGE2) in colonic tissue decreases, and Bifidobacterium spp. (beneficial intestinal microbiota) content increases in the Lipo-IRI-treated group. Moreover, no damage is observed by the hematoxylin and eosin staining of the normal tissue samples from the Lipo-IRI-treated group. In a xenograft mouse model, CRC tumors shrink markedly following Lipo-IRI treatment, and mice receiving a targeted combination of Lipo-IRI and liposomal doxorubicin (Lipo-Dox) extend their survival rate significantly. Overall, our results demonstrate that this formulation of Li...Continue Reading

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Citations

Jul 28, 2020·Nanomaterials·Chunhua Yang, Didier Merlin
Jul 27, 2021·Frontiers in Bioengineering and Biotechnology·Kangkang YingBinbin Xie
Aug 29, 2021·Pharmaceutics·Ana Luiza C de S L OliveiraRaimundo Fernandes de Araújo Junior

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Methods Mentioned

BETA
surgical resection
xenograft
Dynamic Light Scattering
transmission electron microscopy
ELISA

Software Mentioned

Empower
NTA
Zetasizer
GraphPad Prism

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