A novel irinotecan-lipiodol nanoemulsion for intravascular administration: pharmacokinetics and biodistribution in the normal and tumor bearing rat liver.
A novel irinotecan-lipiodol nanoemulsion for intravascular administration: pharmacokinetics and biodistribution in the normal and tumor bearing rat liver.
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DOI：
10.1080/10717544.2020.1869863
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发表时间：
2021-12
期刊：
影响因子：
6
通讯作者：
Tam AL
中科院分区：
文献类型：
--
作者：
Melancon MP;Yevich S;Avritscher R;Swigost A;Lu L;Tian L;Damasco JA;Dixon K;Cortes AC;Munoz NM;Liang D;Liu D;Tam AL
结直肠癌是美国最常见的癌症之一，对于发生肝转移的患者，治疗选择有限。几种化疗方案已用于治疗结直肠肝转移的经血管肝靶向治疗，但没有明确证据表明一种治疗优于另一种治疗。我们描述了一种新型纳米乳剂的开发，该乳剂通过将伊立替康（IRI）（用于治疗结肠癌的一线全身性药物）与阿托碘油（一种源自罂粟籽油的油性造影剂）联合使用，并评价了其作为门静脉化疗栓塞（PVCE）与经动脉化疗栓塞（TACE）递送的函数的药代动力学和生物分布特征。使用Tessari技术来产生稳定的乳液（20 mg IRI与2 mL曲洛多混合），所得粒径范围为28.9 nm至56.4 nm。通过静脉采样在布法罗大鼠中建立的药代动力学特征表明，与IRI单独给药相比，IRI-阿碘油PVCE后IRI的曲线下面积（AUC 0 −∞）显著更小（131 µg*min/mL vs. 316 µg*min/mL，p值= 0.023），表明IRI-阿碘油纳米乳剂通过首过提取在肝脏中的IRI保留量显著更高。随后在荷瘤WAG/Rjj大鼠中进行的生物分布研究显示，与PVCE（29.19 ± 12.33 µg/g vs 3.42 ± 1.62; p值= 0.0033）或IV（29.19 ± 12.33 µg/g vs 1.05 ± 0.47; p值= 0.0035）相比，TACE后肿瘤中存在更多的IRI。IRI-曲洛多纳米乳剂在所有给药途径中均表现出可接受的肝毒性特征。总之，通过TACE的IRI-曲洛多纳米乳剂显示出前景，并值得进一步研究作为治疗转移性结直肠癌的一种选择。
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.
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影响因子：
2.2
作者：
Bretagnol, Frederic;Maggiori, Leon;Panis, Yves
通讯作者：
Panis, Yves
DOI：
10.1016/s1051-0443(96)72880-4
发表时间：
1996-05-01
影响因子：
2.9
作者：
Cay, O;Kruskal, J;Clouse, ME
通讯作者：
Clouse, ME
影响因子：
19.7
作者：
deBaere, T;Zhang, XW;Roche, A
通讯作者：
Roche, A
影响因子：
4.8
作者：
Kan, ZX;Wright, K;Wallace, S
通讯作者：
Wallace, S
影响因子：
8.8
作者：
Guichard, S;Terret, C;Hennebelle, I;Lochon, I;Chevreau, P;Frétigny, E;Selves, J;Chatelut, E;Bugat, R;Canal, P
通讯作者：
Canal, P