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

Authors

Marites P. Melancon, University of Texas MD Anderson Cancer Center
Steven Yevich, University of Texas MD Anderson Cancer Center
Rony Avritscher, University of Texas MD Anderson Cancer Center
Adam Swigost, University of Texas MD Anderson Cancer Center
Linfeng Lu, University of Texas MD Anderson Cancer Center
Li Tian, University of Texas MD Anderson Cancer Center
Jossana A. Damasco, University of Texas MD Anderson Cancer Center
Katherine Dixon, University of Texas MD Anderson Cancer Center
Andrea C. Cortes, University of Texas MD Anderson Cancer Center
Nina M. Munoz, University of Texas MD Anderson Cancer Center
Dong Liang, Texas Southern University
David Liu, The University of British Columbia
Alda L. Tam, University of Texas MD Anderson Cancer Center

Document Type

Article

Publication Date

1-1-2021

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.

Recommended Citation

Melancon, Marites P.; Yevich, Steven; Avritscher, Rony; Swigost, Adam; Lu, Linfeng; Tian, Li; Damasco, Jossana A.; Dixon, Katherine; Cortes, Andrea C.; Munoz, Nina M.; Liang, Dong; Liu, David; and Tam, Alda L., "A novel irinotecan-lipiodol nanoemulsion for intravascular administration: pharmacokinetics and biodistribution in the normal and tumor bearing rat liver" (2021). Faculty Publications. 46.
https://digitalscholarship.tsu.edu/facpubs/46