著者

佐塚 泰之 廣津 祥代 広田 貞雄 金川 麻子 森田 哲生

出版者

日本DDS学会

雑誌

Drug Delivery System (ISSN:09135006)

巻号頁・発行日

vol.13, no.6, pp.415-421, 1998-11-10 (Released:2009-01-21)

参考文献数

19

被引用文献数

1 1

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We prepared the liposomes, changed the entrapped amount of adriamycin (ADR) per the amount of liposome composing lipid, and after the addition of these liposomes with the same concentration of ADR(therefore, different dose of lipid), the tumor cell uptake of ADR was examined. The high entrapped amount of ADR demonstrated the usefulness in the tumor cell uptake of the ADR liposome in vitro. The cell uptake of the liposome depended on additional amount of ADR and liposomal lipid. Next, using ADR contained liposome and irinotecan contained liposome, its usefulness on tumor cell uptake by the polyethyleneglycol (PEG) modification of the surface on the liposome in vitro examined. In both liposome, PEG modification of the surface on the liposome facilitated the initial rate of the liposome uptake into the tumor cell. We have considered that this facilitation was attributed to the lipo-hydrophilic property of PEG and the fixed aqueous layer around the liposome. Therefore, PEG modification of the surface on the liposome, prevents the adhesion of serum opsonine and avoids reticuloendothelial system, does not inhibit tumor cell uptake rather facilitates. From the results of dextran sulfate contained liposome, it is expected that these liposome passed through the membrane of the tumor cell. Therefore, a higher entrapped amount of antitumor agents in the liposome and PEG modification have been confirmed to be beneficial in the tumor cell uptake.

著者

佐塚 泰之 廣津 祥代 宮城島 惇夫 野澤 靖夫 広田 貞雄

出版者

日本DDS学会

雑誌

Drug Delivery System (ISSN:09135006)

巻号頁・発行日

vol.12, no.3, pp.193-198, 1997-05-10 (Released:2009-01-21)

参考文献数

15

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The lipid composition, particle diameter and dose have been reported to affect the liposomal uptake in the tumor. However, effects of encapsulation amount of drugs in liposomes on the uptakes have scarecely been reported either in vitro or in vivo. In this study, we examined the uptake of liposomes containing CPT-11 by Ehrlich ascites carcinoma in vitro changing the encapsulation amount of CPT-11, and also the tissue distribution of liposomal CPT-11 in vivo with mice. After the addition of high concentration as CPT-11, the uptakes in the tumor cell by liposomes was about 1/3 of that by the solution in vitro. However, after the addition of same level as tissue distribution of CPT-11 in vivo, there is no difference on CPT-11 uptakes between liposome and solution. Thus lipid satulation in the tumor cells was observed by increasing liposomes in the medium. For a definite dose, the decrease of CPT-11 amount in the liposomes reduced the uptake in the tumor cell. Therefore, we thought that the uptake of liposomes in the tumor cell depended on lipid amount of liposomes. The increase of CPT-11 amount in the liposomes enhanced CPT-11 concentration in the serum, liver and tumor after administration of liposomal CPT-11 to the mice. An enhanced antitumor activity was expected from the result of SN-38 concentration in the tumor.