Efficient gram-scale continuous production of near-infrared-sensitive liposomes for light-triggered delivery of polyinosinic-polycytidylic acid

Liposomes can be used as drug carriers, biocompatible with human cells. However, efficient on-demand release of the liposome payload still remains a challenge. Also, sophisticated liposome formulations, such as those encapsulating one or more drugs together with a suitable compound to facilitate triggered release, are usually prepared in complex multistep batch procedures with low (e.g. milligram) production rates. The aim of this work is to develop a continuous supercritical CO2 based scalable process for the production of near-infrared (NIR) light-sensitive liposomes. Hollow Gold Nanospheres (HGN), about 5 nun large, have been synthesized as light sensitive agents for triggered release and, then, they were embedded in controlled size liposomes (from 0.75 +/- 0.19 mu m to 1.76 +/- 0.71 mu m) together with biological active compounds Polyinosinic-polycytidylic Acid (PIC) and Bovine Serum Albumin (BSA), using a supercritical assisted process. High encapsulation efficiency of all components, up to 95%, with a gram-scale production of 1 g/h of HGN loaded liposomes have been obtained. Drug release tests verified that NIR light could be efficiently used as a stimulus on these vectors to achieve drug release on-demand. Produced liposomes presented high biocompatibility.