A novel irinotecan-lipiodol nanoemulsion for intravascular administration: pharmacokinetics and biodistribution in the normal and tumor bearing rat liver

Marites P. Melancon, Steven Yevich, Rony Avritscher, Adam Swigost, Linfeng Lu, Li Tian, Jossana A. Damasco, Katherine Dixon, Andrea C. Cortes, Nina M. Munoz, Dong Liang, David Liu, Alda L. Tam

Research output: Contribution to journalArticlepeer-review

Abstract

Colorectal cancer is one of the most common cancers in the United States and treatment options are limited for patients who develop liver metastases. Several chemotherapeutic regimens have been used for transvascular liver-directed therapy in the treatment of colorectal liver metastases without clear evidence of superiority of one therapy over another. We describe the development of a novel nanoemulsion through combining irinotecan (IRI), a first line systemic agent used for the treatment of colon cancer, with lipiodol, an oily contrast medium derived from poppy seed oil, and evaluated its pharmacokinetic and biodistribution profile as a function of portal venous chemoembolization (PVCE) versus transarterial chemoembolization (TACE) delivery. The Tessari technique was used to create a stable emulsion (20 mg IRI mixed with 2 mL lipiodol) with resultant particle size ranging from 28.9 nm to 56.4 nm. Pharmacokinetic profile established through venous sampling in Buffalo rats demonstrate that the area under the curve (AUC0−∞) of IRI was significantly less after PVCE with IRI-lipiodol as compared to IRI alone (131 vs. 316 µg*min/mL, p-value =.023), suggesting significantly higher amounts of IRI retention in the liver with the IRI-lipiodol nanoemulsion via first-pass extraction. Subseqent biodistribution studies in tumor-bearing WAG/Rjj rats revealed more IRI present in the tumor following TACE versus PVCE (29.19 ± 12.33 µg/g versus 3.42 ± 1.62; p-value =.0033) or IV (29.19 ± 12.33 µg/g versus 1.05 ± 0.47; p-value =.0035). The IRI-lipiodol nanoemulsion demonstrated an acceptable hepatotoxicity profile in all routes of administration. In conclusion, the IRI-lipiodol nanoemulsion via TACE showed promise and warrants further investigation as an option for the treatment of metastatic colorectal cancer.

Original languageEnglish (US)
Pages (from-to)240-251
Number of pages12
JournalDrug delivery
Volume28
Issue number1
DOIs
StatePublished - 2021

Keywords

  • Nanoparticles
  • biodistribution
  • drug delivery
  • emulsion
  • irinotecan
  • lipiodol
  • pharmacokinetics

ASJC Scopus subject areas

  • Pharmaceutical Science

MD Anderson CCSG core facilities

  • High Resolution Electron Microscopy Facility

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