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

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 degrees C to 70 degrees 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. (C) 2020 Elsevier B.V. All rights reserved.