Optimizing drug distribution by emulsifying lipophilic platinum derivative

• Project/Area Number: 17K16489
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: Nippon Medical School
• Principal Investigator: Yasui Daisuke 日本医科大学, 医学部, 助教 (00755001)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 肝細胞癌 / 経皮的肝動脈化学塞栓術 / エマルジョン / 肝動脈化学塞栓術 / 単分散 / 抗癌剤 / 乳膜化 / 膜乳化 / IVR

Outline of Final Research Achievements

Development of a novel embolization agent for transcatheter arterial chemoembolization: a pivotal treatment for inoperable hepatocellular carcinoma, was attempted in this study. Monodisperse s/ow emulsion of Miriplatin and Lipiodol was successfully obtained by performing direct emulsification method using Shirasu porous glass membrane and adding polyoxyethylene hydrogenated castor oil 60 as a surfactant. Better intra-tumoral accumulation and retention was observed with this novel emulsion, compared to conventional suspension in animal experiment. Incidence of adverse events was less frequent in s/o/w emulsion group, compared to suspension group.

Academic Significance and Societal Importance of the Research Achievements

本研究において、新たな塞栓物質である単分散系エマルジョンを使用することにより、肝細胞癌に対するカテーテル治療の成績が向上する可能性が示唆された。肝細胞癌の患者のうち、手術やラジオ波焼灼術などの根治治療の適応となる方は限られているため、本研究の臨床応用により肝細胞癌全体の治療成績の向上が期待できる。また近年では大腸癌や膵癌からの転移性肝腫瘍の患者が増えているが、本研究の成果を応用することにより、これらの疾患においても予後改善が期待できるものと考える。

Research Products

• [Journal Article] Efficacy and safety of a monodisperse solid-in-oil-in-water emulsion in transcatheter arterial chemoembolization in a rabbit VX2 tumor model (2019)
  • Author(s): Yasui Daisuke、Yamane Aya、Itoh Hiroshi、Kobayashi Masayuki、Kumita Shin-ichiro
  • Journal Title: bioRxiv Volume: -
  • DOI: 10.1101/759316
  • Open Access
• [Journal Article] Novel treatment strategy for advanced hepatocellular carcinoma: combination of conventional transcatheter arterial chemoembolization and modified method with portal vein occlusion for cases with arterioportal shunt: a preliminary study. (2018)
  • Author(s): Yasui D, Ueda T, et al.
  • Journal Title: Acta Radiologica Volume: 59(3) Issue: 3 Pages: 266-274
  • DOI: 10.1177/0284185117717762
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of the relationship between hepatocellular carcinoma location and transarterial chemoembolization efficacy. (2017)
  • Author(s): Miki I, Ueda T, et al.
  • Journal Title: World Journal of Gastroenterolgy Volume: 23(35) Issue: 35 Pages: 6437-6447
  • DOI: 10.3748/wjg.v23.i35.6437
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Endovascular Treatment Strategy Using Catheter-Directed Thrombolysis, Percutaneous Aspiration Thromboembolectomy, and Angioplasty for Acute Upper Limb Ischemia (2017)
  • Author(s): Ueda T, Murata S, Miki I, Yasui D, Sugihara F, Tajima H, Morota T, Kumita S
  • Journal Title: Cardiovascular and Interventional Radiology Volume: 印刷中 Issue: 7 Pages: 978-986
  • DOI: 10.1007/s00270-017-1599-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] VX2担癌ウサギを用いた単分散系ミリプラチン懸濁液の安全性と有効性に関する検討 (2019)
  • Author(s): 安井 大祐、村田 智、上田 達夫、杉原 史恵、斎藤 英正、伊藤 博、小林 正行、汲田 伸一郎
  • Organizer: 日本IVR学会総会
• [Presentation] Initial experience of a novel drug delivery system for anticancer agent: monodisperse solid-in-oil-in-water emulsion using VX-2 tumor bearing rabbits (2019)
  • Author(s): Daisuke Yasui, Satoru Murata, Tatsuo Ueda, Fumie Sugihara, Hidemasai Saito, Izumi Tanaka, Sayaka Shirai, Hiroshi Itoh, Masayuki Kobayashi, Aya Yamane, Shin-ichiro Kumita
  • Organizer: CIRSE
  • Int'l Joint Research
• [Presentation] Novel treatment strategy for locally-advanced hepatocellular carcinoma (2018)
  • Author(s): Daisuke Yasui
  • Organizer: JSIR & ISIR 2018
  • Int'l Joint Research
• [Presentation] Percutaneous intervention for tricuspid valve vegetation under (2018)
  • Author(s): Daisuke Yasui,Tatsuo Ueda,Fumie Sugihara,Hidemasa Saitou,Izumi Tanaka,Yasuo Miyagi,Satoru Murata, Hiroyuki Tajima,Shin-ichiro Kumita
  • Organizer: 12th Symposium of the Japanese Scandinavian Radiological Society
  • Int'l Joint Research
• [Presentation] 産科的処置にて制御困難な産科出血に対する経皮的動脈塞栓術の有用性 (2017)
  • Author(s): 安井大祐、村田智、上田達夫、杉原史恵、齊藤英正、米澤美令、竹下俊行、汲田伸一郎
  • Organizer: 日本IVR学会総会
• [Presentation] Endovascular treatment for post-operative bleeding after hepato-pancreato-biliary surgery (2017)
  • Author(s): Daisuke Yasui, Satoru Murata, Tatsuo Ueda, Fumie Sugihara,Hidemasa Saitou, Nobuhiko Taniai, Eiji Uchida, Shin-ichiro Kumita
  • Organizer: IASGO world congress 2017
  • Int'l Joint Research