Flow process of bioadhesive liposome production using supercritical-segmented solution

• Project/Area Number: 18H01773
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 27020:Chemical reaction and process system engineering-related
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: Shimoyama Yusuke 東京工業大学, 物質理工学院, 教授 (30403984)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2020: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
• Keywords: 超臨界二酸化炭素 / フロープロセス / リポソーム / 微小流路 / リポソーム形成 / 超臨界流体 / 相分離 / スラグ流 / マイクロ流路

Outline of Final Research Achievements

Flow-type fabrication method of liposome was developed by using flow state of supercritical carbon dioxide in microfluid system. This flow-type process was extended to the fabrication of PEGylated liposome. It is found that the structured-liposome can be formed in this flow-type process. Size of liposome can be controlled largely using ethanol as solvent for lipid in the flow-type process. Also, the fabrication process of PEGylated liposome in Post-Tube process allows to reduce the particle size of liposome and increase the encapsulation efficiency compared with those by the batch-type process.

Academic Significance and Societal Importance of the Research Achievements

超臨界二酸化炭素を利用することで，人体に有害となる有機溶媒の使用量を大幅に低減でき，かつ連続的なリポソームの生成プロセスを構築した点は，安全かつ低価格な医薬品，化粧品の製造への応用が期待され，社会的な意義がある．本研究課題における微小流路での流動状態，ならびに微量流路におけるリポソームの構造化は，超臨界二酸化炭素の新たな技術展開として学術的意義がある．

Research Products

• [Journal Article] Flow patterns in microfluidic system of CO2 + 1-propanol, ethanol, methanol, and hexane binary mixtures at high pressures (2020)
  • Author(s): Peany Houng, Yuya Murakami, Yusuke Shimoyama
  • Journal Title: Chemical Engineering Journal Volume: 394 Pages: 124891-124891
  • DOI: 10.1016/j.cej.2020.124891
  • Peer Reviewed
• [Journal Article] Effect of Slug Flow Pattern on Supercritical Extraction of Phenolic Compounds from Aqueous Solutions (2020)
  • Author(s): Peany Houng, Yuya Murakami, Yusuke Shimoyama
  • Journal Title: The Journal of Supercritical Fluids Volume: in press Pages: 104885-104885
  • DOI: 10.1016/j.supflu.2020.104885
  • Peer Reviewed
• [Presentation] 超臨界エマルション抽出法を利用したポリカプロラクトンナノ分散液の作製 (2021)
  • Author(s): Bao Qiuqi，織田耕彦，下山裕介
  • Organizer: 化学工学会第86年会
• [Presentation] Effect of pressure and surfactant on formation of solid lipid particles using supercritical fluid extraction of emulsion (2021)
  • Author(s): Wijakmatee Thossaporn，織田耕彦，下山裕介
  • Organizer: 化学工学会第86年会
• [Presentation] 超臨界二酸化炭素相と界面を利用した材料プロセス (2020)
  • Author(s): 下山裕介
  • Organizer: 化学工学会第51回秋季大会
  • Invited
• [Presentation] 超臨界エマルション抽出における相挙動解析と抽出機構の解明 (2019)
  • Author(s): 鳥田勇介，村上裕哉，下山裕介
  • Organizer: 分離技術会年会2019
• [Presentation] Supercritical micro-flow extraction of phenolic compounds from aqueous solution: Effect of residence time (2019)
  • Author(s): Peany Houng, Yuya Murakami, Yusuke Shimoyama
  • Organizer: 分離技術会年会2019
• [Presentation] 超臨界二酸化炭素による界面フロープロセスを利用したリポソーム生成 (2019)
  • Author(s): 井上渓汰，秋山龍之介，村上裕哉，下山裕介
  • Organizer: 化学工学会横浜大会
• [Presentation] Flow production of functionalized liposome using supercritical carbon dioxide and microfluid system (2019)
  • Author(s): Yuya Murakami, Keita Inoue, Yusuke Shimoyama
  • Organizer: Asian Pacific Confederation of Chemical Engineering 2019
  • Int'l Joint Research
• [Presentation] Investigation of flow patterns in microfluidic system for binary and ternary systems (2019)
  • Author(s): Peany Houng, Yuya Murakami, Yusuke Shimoyama
  • Organizer: Asian Pacific Confederation of Chemical Engineering 2019
  • Int'l Joint Research
• [Presentation] Flow production of nanosuspension in supercritical CO2 (2019)
  • Author(s): Yusuke Shimoyama
  • Organizer: Supergreen 2019
  • Int'l Joint Research / Invited
• [Presentation] Mass transfer analysis on supercritical fluid extraction of emulsion using image analysis of phase behavior (2019)
  • Author(s): Yuya Murakami, Yusuke Torita, Yusuke Shimoyama
  • Organizer: IMPRES2019
  • Int'l Joint Research
• [Presentation] 超臨界エマルション抽出を利用した疎水性化合物分散溶液の作製と物質移動解析 (2019)
  • Author(s): 村上裕哉，鳥田勇介，下山裕介
  • Organizer: 化学工学会第84年会
• [Presentation] Oil phase swelling and extraction mechanism during supercritical fluid emulsion extraction via phase behavior observation (2018)
  • Author(s): Yuya Murakami, Yusuke Torita, Yusuke Shimoyama
  • Organizer: 8th International Symposium on Molecular Thermodynamics and Molecular Simulation
  • Int'l Joint Research
• [Presentation] 画像解析を用いた超臨界エマルション抽出における物質移動解析 (2018)
  • Author(s): 村上裕哉，鳥田勇介，下山裕介
  • Organizer: 化学工学会第50回秋季大会
• [Presentation] Nobel production of liposome in a continuous manner using micro-mixer and supercritical carbon dioxide (2018)
  • Author(s): Yuya Murakami, Yusuke Torita, Yusuke Shimoyama
  • Organizer: 6th International Workshop on Process Intensification