Preparation of Lecithin Microcapsules by a Dilution Method Using the Wurster Process for Intraarterial Administration in Gadolinium Neutron Capture Therapy
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概要
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Lecithin microcapsules containing gadolinium (Gd) were designed and prepared as a dosage form for intraarterial administration to accumulate Gd in tumors in neutron capture therapy. The microcapsules were composed of 1) a lactose core, 2) a layer of distearylamide of gadopentetic acid (Gd-DTPA-SAm) and polyvinylpyrrolidone (PVP) with or without soybean lecithin (SL) and 3) a membrane containing SL, cholesterol, stearic acid and PVP at three different compositions. A dilution method using the Wurster process was developed for small-scale preparation. In spite of using only 2 g of Gd-DTPA-SAm each, three types of microcapsules wewe obtained with a content of 24.9% as Gd-DTPA-SAm (3.66% as Gd) even at 150% coating level. The swelling type of microcapsules (MC-D1) did not release Gd at all for the entire 120 min of the experiment in a 0.9% saline solution. On the other hand, the rapid-erosion type (MC-D2) and the vesicle-dispersing type (MC-D3) released Gd with a lag time. The percent released depended on the coating level and the SL content in the Gd-fixing layer. A large number of droplet-like particles spouted out, and/or tubular vesicles formed with MC-D2 and MC-D3 in the saline solution. These phenomena implied that the water-insoluble Gd-DTPA-SAm would be entrapped in these particles/vesicles. When MC-D2 and MC-D3 were administered to normal rats via the hepatic artery, a Gd-accumulation as high as 70 and 71% of the injected dose was detected in the whole liver 2 h after administration. In addition, biochemical and histological evaluation of the liver after administration indicated that embolization of the microcapsules actually occurred in the blood vessels, and that necrosis induced by ischemia was not serious. These results suggested that administration of these microcapsules might be multiply repeated in order to accumulate the required amount of Gd in tumors.
- 公益社団法人日本薬学会の論文
- 1999-01-15
著者
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市川 秀喜
神戸学院大学薬学部
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市川 秀喜
神戸学院大学薬学部物性薬学部門製剤学研究室 同ライフサイエンス産学連携研究センター
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AKINE Yasuyuki
Institute of Clinical Medicine,University of Tsukuba
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Akine Y
Institute Of Clinical Medicine University Of Tsukuba
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Akine Yasuyuki
Institute Of Clinical Medicine University Of Tsukuba
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FUKUMORI Yoshinobu
Faculty of Pharmaceutical Sciences, Kobe-Gakuin University
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TOKUUYE Koichi
Department of Radiation Oncology, University of Tsukuba
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福森 義信
神戸学院大学 薬学部
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Fukumori Yoshinobu
Faculty Of Pharmaceutical Sciences Kobe-gakuin University
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Fukumori Yoshinobu
Faculty Of Pharmaceutical Science Kobe Gakuin University
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ICHIKAWA Hideki
Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin Uni
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Ichikawa Hideki
Department Of Physical Pharmacy Kobe Gakuin University
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Ichikawa Hideki
Faculty Of Pharmaceutical Science Kobe Gakuin University
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Tokuuye Koichi
Department Of Radiation Therapy The National Cancer Hospital
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Tokuuye Koichi
Department Of Radiation Oncology Graduate School Of Comprehensive Human Sciences University Of Tsuku
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JONO KAORI
Faculty of Pharmaceutical Sciences, Kobe Gakuin University
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Jono Kaori
Faculty Of Pharmaceutical Sciences Kobe Gakuin University
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FUJIOKA Kazuhiro
Faculty of Pharmaceutical Sciences, Kobe Gakuin University
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Fujioka Kazuhiro
Faculty Of Pharmaceutical Sciences Kobe Gakuin University
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