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

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  • Additional Information
    • Source:
      Publisher: Taylor & Francis Country of Publication: England NLM ID: 9417471 Publication Model: Print Cited Medium: Internet ISSN: 1521-0464 (Electronic) Linking ISSN: 10717544 NLM ISO Abbreviation: Drug Deliv Subsets: MEDLINE
    • Publication Information:
      Publication: 2015->: Abingdon, Oxford : Taylor & Francis
      Original Publication: Orlando, FL : Academic Press, c1993-
    • Subject Terms:
      Hepatic Artery* ; Portal Vein*; Colorectal Neoplasms/*pathology ; Ethiodized Oil/*pharmacokinetics ; Irinotecan/*pharmacokinetics ; Liver/*metabolism ; Liver Neoplasms/*secondary ; Topoisomerase I Inhibitors/*pharmacokinetics; Animals ; Cell Line, Tumor ; Chemoembolization, Therapeutic/methods ; Drug Carriers ; Emulsions/pharmacokinetics ; In Vitro Techniques ; Irinotecan/administration & dosage ; Liver Neoplasms/therapy ; Nanostructures ; Prodrugs/administration & dosage ; Prodrugs/pharmacokinetics ; Rats ; Topoisomerase I Inhibitors/administration & dosage
    • 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 (AUC 0-∞ ) 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.
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    • Grant Information:
      P30 CA016672 United States CA NCI NIH HHS; R01 HL141831 United States HL NHLBI NIH HHS
    • Contributed Indexing:
      Keywords: Nanoparticles; biodistribution; drug delivery; emulsion; irinotecan; lipiodol; pharmacokinetics
    • Accession Number:
      0 (Drug Carriers)
      0 (Emulsions)
      0 (Prodrugs)
      0 (Topoisomerase I Inhibitors)
      7673326042 (Irinotecan)
      8008-53-5 (Ethiodized Oil)
    • Publication Date:
      Date Created: 20210127 Date Completed: 20210906 Latest Revision: 20220406
    • Publication Date:
      20240105
    • Accession Number:
      PMC8725905
    • Accession Number:
      10.1080/10717544.2020.1869863
    • Accession Number:
      33501859