One-step Production of Sterically Stabilized Anionic Nanoliposome Using Microfluidic Device.

Anionic liposomes (AL) are very attractive for nanomedicine and some formulations have already been launched for clinical development. Despite the excellent potential, their application presents two major challenges: laborious production methods and rapid degradation and elimination from blood by the immune system. In this work, we optimized the production of AL and its stealth form (SAL) using a onestep microfluidic process. We obtained unilamellar and near-monodisperse (< 10%) AL composed by the commercial composition (DMPC:DMPG) with mean size small as 53.7 nm, which is optimized for application in drug delivery. We also obtained SAL with similar characteristics using the microfluidic technique, overcoming the limitation of conventional methods where SAL presents high polydispersity (> 30%). This study demonstrates the great potential of the microfluidic technique for one-step production of stealth anionic nanoliposomes with controlled sizes and reproducible characteristics.

3D micromixer for nanoliposome synthesis: a promising advance in high mass productivity.

This paper addresses an important breakthrough in the high mass production of liposomes by microfluidics technology. We investigated the synthesis of liposomes using a high flow rate microfluidic device (HFR-MD) with a 3D-twisted cross-sectional microchannel to favor chaotic advection. A simple construction scaffold technique was used to manufacture the HFR-MD. The synthesis of liposomes combined the effects of high flow and high concentration of lipids, resulting in high mass productivity (2.27 g of lipid per h) which, to our knowledge, has never been registered by only one microdevice. We assessed the effects of the flow rate ratio (FRR), total flow rate (TFR), and lipid concentration on the liposome physicochemical properties. HFR-MD liposomes were monodisperse (0.074) with a size around 100 nm under the condition of an FRR of 1 (50% v/v ethanol) and TFR of 5 ml min-1 (expandable to 10 ml min-1). We demonstrated that the mixing conditions are not the only parameter controlling liposome synthesis using experimental and computational fluid dynamics analysis. A vacuum concentrator was used for ethanol removal, and there is no further modification after processing in accordance with the structural (SAXS) and morphological (cryo-TEM) analysis. Hence, the HFR-MD can be used to prepare nanoliposomes. It emerges as an innovative tool with high mass production.