Rapid production of liposomes using high pressure carbon dioxide and direct ultrasonication

• Published in: The Journal of supercritical fluids 2020-06, Vol.160, p.104782, Article 104782
• Main Authors: Tokunaga, Shinichi, Tashiro, Hiroyuki, Ono, Kento, Sharmin, Tanjina, Kato, Takafumi, Irie, Keiichi, Mishima, Kenichi, Satho, Tomomitsu, Aida, Taku Michael, Mishima, Kenji
• Format: Article
• Language: English
• Subjects: Drug delivery; High pressure carbon dioxide; Non-solvent method; Ultrasonic irradiation
• ISSN: 0896-8446; 1872-8162
• DOI: 10.1016/j.supflu.2020.104782

[Display omitted] •Non-solvent method using high pressure carbon dioxide and direct ultrasonication.•Production of nano-sized liposomes with high yields.•Visual observation of high pressure cell during liposome formation.•Mechanisms for liposome formation. Herein, we introduce a protocol for preparing liposomes using high-pressure CO2, water and direct ultrasonication (HPC-D) allowing rapid formation of liposomes in a single-step. In the HPC-D method, phospholipid suspensions were treated at temperatures from 25 °C to 70 °C and pressures from 4 MPa to 6.8 MPa with direct ultrasonication. The liposomes produced from HPC-D had an average particle size of 159 ± 2 nm to 136 ± 8 nm at liposome recovery yields up to 95.3 ± 4.6 %. A mechanism for the HPC-D method is proposed, in which the micro-phase separation between water-CO2 interface increases surface area and phospholipids act as surfactants and reassemble into small liposome particles. Drug loading (DL) and encapsulation efficiency (EE) of liposomes obtained with the HPC-D method for Cyclosporin A gave DL values of 37.4 ± 3.4 % and EE of 79.7 ± 2.5 %, confirming efficient entrapment.