Continuous Microinstillation of Phenol Red on Liver Surface for Liver Site-Selective Delivery.

Nakamura, Junzo; Yoshida, Yoshiharu; Mera, Kunihiro; Mukai, Takahiro; Nishida, Koyo; Sasaki, Hidetada

doi:10.1248/bpb.22.713

Cited by 21 publications

(21 citation statements)

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“…[51][52][53][54][55] However, it is difficult to achieve lung site-selective gene transfection using pDNA/cationic liposome complexes after intravenous administration because they are distributed throughout the whole lung and body via the blood stream. It is recognized that drugs are adequately absorbed by the liver, [17][18][19][20][21][22][23][24][25][26] kidneys [27][28][29][30][31] and stomach [32][33][34] surfaces and accumulate organ-and site-selectively in rats. For gene transfer, we previously reported on liver- [35][36][37][38] and kidney-selective 39) gene expression after organ surface instillation of naked pDNA in mice.…”

Section: Resultsmentioning

confidence: 99%

“…We previously developed a method for the application of drugs onto the surface of intraperitoneal organs such as the liver, [17][18][19][20][21][22][23][24][25][26] kidney, [27][28][29][30][31] and stomach [32][33][34] in rats and found it to be a useful method for site-selective drug delivery to these organs. Furthermore, we reported on site-selective gene expression following the instillation of naked pDNA onto the liver surface [35][36][37][38] and kidney surface 39) in mice.…”

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confidence: 99%

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Unilateral Lung-Selective Gene Transfer Following the Administration of Naked Plasmid DNA onto the Pulmonary Pleural Surface in Mice

Nakamura

Fumoto

Ariyoshi

et al. 2007

Biological & Pharmaceutical Bulletin

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Unilateral Lung-Selective Gene Transfer Following the Administration of Naked Plasmid DNA onto the Pulmonary Pleural Surface in Mice

Nakamura

Fumoto

Ariyoshi

et al. 2007

Biological & Pharmaceutical Bulletin

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“…[13][14][15][16][17][18][19][20]23) Because 5-FU is mostly catabolized and inactivated by DPD, 28) we expected that combining DPD inhibitors enable us to increase 5-FU availability at the admin- istration site. In this study, we chose gimeracil and uridine as candidates for promising DPD inhibitors that can be applied to the rat liver surface.…”

Section: Discussionmentioning

confidence: 99%

“…[13][14][15][16][17][18] To use this route as a local HCC therapy, we showed that 5-fluorouracil (5-FU), a pyrimidine anticancer drug, was site-selectively and continuously delivered in the liver after application to the liver surface in rats. 19,20) We have also investigated other organs as an administration route of 5-FU.…”

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confidence: 99%

Effect of Metabolic Inhibitors on the Hepatic Disposition of 5-Fluorouracil after Application to the Rat Liver Surface

Shimokawa

Wakasugi

Tomonaga

et al. 2016

Biological & Pharmaceutical Bulletin

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We evaluated the effects of 5-fluorouracil (5-FU) metabolic inhibitors, gimeracil or uridine, on the hepatic disposition of 5-FU after application to the liver surface in rats, aiming to enhance the availability of 5-FU in the liver. 5-FU solution with or without metabolic inhibitors was applied to the rat liver surface using a cylindrical diffusion cell. The liver, blood and the remaining solution in the diffusion cell were collected at specified times, and assayed for 5-FU content. 5-FU absorption properties were not altered by addition of gimeracil and uridine. The 5-FU concentration in the diffusion cell attachment site of the rat liver (site 1) at 0.1-0.4 M ratios of gimeracil to 5-FU was significantly higher than that of the control. On the contrary, the addition of uridine did not increase the 5-FU concentration at site 1. At a 0.1 M ratio of gimeracil to 5-FU, the maximum 5-FU plasma concentration was the lowest, and the area under the 5-FU concentration-time curve at site 1 was 3.4 times greater than that of the control. We demonstrated that applying 5-FU with gimeracil to the rat liver surface could increase the availability of 5-FU in the liver.Key words liver surface; 5-fluorouracil; disposition; dihydropyrimidine dehydrogenase; gimeracil; uridine Hepatocellular carcinoma (HCC) is the second most frequent cause of cancer-related death worldwide. 1) In many cases, chronic hepatitis and hepatic cirrhosis trigger the development of HCC. 2) Even radical surgery, a potentially curative treatment for HCC, is limited by cancer progression and hepatic functional reserve. 3) In addition, HCC frequently recurs after radical surgery in the residual liver tissue because of progressive disease. 4) Although chemotherapy has been applied to treat the advanced or recurrent HCC, most of anticancer drugs cannot exert the desired effect on HCC because of high chemoresistance rate. 5,6) Local therapies such as percutaneous ethanol injection, 7,8) intratumoral injection 9-11) and intra-arterial infusion 12) have been performed to enhance the therapeutic effect of anticancer drugs on HCC. However, optimal delivery of anticancer drugs to HCC lesion is difficult through these routes because of distribution in the normal surrounding tissue or rapid efflux into the systemic circulation from the injection site.Therefore, we have proposed that the liver surface is a new drug administration route, and investigated the absorption and disposition characteristics of several marker compounds after direct application to the rat liver surface. [13][14][15][16][17][18] To use this route as a local HCC therapy, we showed that 5-fluorouracil (5-FU), a pyrimidine anticancer drug, was site-selectively and continuously delivered in the liver after application to the liver surface in rats. 19,20) We have also investigated other organs as an administration route of 5-FU. 21,22) Although viscous additives to 5-FU solution improved site-selective accumulation of 5-FU, 23) the increase in 5-FU concentration at the application site was not large ...

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“…We previously developed a method for the application of drugs onto the surface of the intraperitoneal organs such as the liver, [14][15][16][17][18][19][20][21][22][23][24] kidney, [25][26][27][28][29] and stomach [30][31][32] in rats and found it to be a useful method for site-selective drug delivery to these organs. Furthermore, we reported on site-selective gene expression following the instillation of naked pDNA onto the liver surface [33][34][35][36] and kidney surface 37) in mice.…”

mentioning

confidence: 99%

Spleen-Selective Gene Transfer Following the Administration of Naked Plasmid DNA onto the Spleen Surface in Mice

Nakamura

Fumoto

Kawanami

et al. 2007

Biological & Pharmaceutical Bulletin

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Continuous Microinstillation of Phenol Red on Liver Surface for Liver Site-Selective Delivery.

Cited by 21 publications

References 0 publications

Unilateral Lung-Selective Gene Transfer Following the Administration of Naked Plasmid DNA onto the Pulmonary Pleural Surface in Mice

Unilateral Lung-Selective Gene Transfer Following the Administration of Naked Plasmid DNA onto the Pulmonary Pleural Surface in Mice

Effect of Metabolic Inhibitors on the Hepatic Disposition of 5-Fluorouracil after Application to the Rat Liver Surface

Spleen-Selective Gene Transfer Following the Administration of Naked Plasmid DNA onto the Spleen Surface in Mice

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