A novel irinotecan-lipiodol nanoemulsion for intravascular administration: pharmacokinetics and biodistribution in the normal and tumor bearing rat liver
| Autor: | Alda L. Tam, Linfeng Lu, Dong Liang, Li Tian, Andrea Cortes, Jossana A. Damasco, Adam Swigost, Marites P. Melancon, Rony Avritscher, Nina M. Muñoz, Steven Yevich, David T.L. Liu, K. Dixon |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Biodistribution
Colorectal cancer Pharmaceutical Science lipiodol 02 engineering and technology RM1-950 Pharmacology In Vitro Techniques Irinotecan 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Ethiodized Oil Hepatic Artery Pharmacokinetics Cell Line Tumor Medicine Animals Prodrugs Chemoembolization Therapeutic biodistribution emulsion Drug Carriers business.industry Portal Vein Liver Neoplasms Treatment options General Medicine 021001 nanoscience & nanotechnology medicine.disease Nanostructures Rats Liver Rat liver Drug delivery drug delivery Lipiodol Nanoparticles Emulsions Therapeutics. Pharmacology Topoisomerase I Inhibitors 0210 nano-technology business Colorectal Neoplasms pharmacokinetics medicine.drug Research Article |
| Zdroj: | Drug Delivery article-version (VoR) Version of Record Drug Delivery, Vol 28, Iss 1, Pp 240-251 (2021) |
| ISSN: | 1521-0464 1071-7544 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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