Liposomal irinotecan for treatment of colorectal cancer in a preclinical model

Jiao Ren Huang, Mei Hsien Lee, Wen Shan Li, Han Chun Wu

Research output: Contribution to journalArticle

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 Lipo-IRI shows a great potential for the treatment of colorectal cancer.

Original languageEnglish
Article number281
JournalCancers
Volume11
Issue number3
DOIs
Publication statusPublished - Mar 1 2019

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irinotecan
Colorectal Neoplasms
Therapeutics
Gastrointestinal Contents

Keywords

  • Colorectal cancer
  • Combination targeted therapy
  • Drug delivery system
  • Liposomal irinotecan
  • Microbiota

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Liposomal irinotecan for treatment of colorectal cancer in a preclinical model. / Huang, Jiao Ren; Lee, Mei Hsien; Li, Wen Shan; Wu, Han Chun.

In: Cancers, Vol. 11, No. 3, 281, 01.03.2019.

Research output: Contribution to journalArticle

Huang, Jiao Ren ; Lee, Mei Hsien ; Li, Wen Shan ; Wu, Han Chun. / Liposomal irinotecan for treatment of colorectal cancer in a preclinical model. In: Cancers. 2019 ; Vol. 11, No. 3.
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