Properties of Liposomes Containing Natural and Synthetic Lipids Formed by Microfluidic Mixing

Abstract

Vesicle formation by a staggered herringbone microfluidic mixer is investigated in comparison to a sonication‐extrusion method. Experiments focused on the incorporation efficiency of lipid components, on dye entrapment efficiency, and on the barrier properties of the vesicle bilayers produced. The microfluidic method produces vesicles largely under the control of thermodynamic factors. As a result, the molecular parameters of the lipids (chain length, chain volume, head group area) directly control vesicle diameter. A hydrophobic branched chain sulfonate lipid is incorporated by microfluidic mixing but not by sonication‐extrusion. The vesicles produced by microfluidic mixing can be used to study ion transport by known ionophores and appear to have directly comparable barrier properties to those produced by sonication‐extrusion. Vesicles containing the branched chain sulfonate are highly permeable. The microfluidic mixing method produces predominantly unilamellar vesicles. Practical Applications: The microfluidic device examined offers a new method to reproducibly produce vesicles that are directly controlled by the molecular components of the lipid mixture. The authors show that this method produces vesicles that are equivalent to currently used methods in the study of synthetic ion channels and carriers. Looking forward, thermodynamically controlled self‐assembly will find application in the creation of new membrane systems and assemblies where the vesicles themselves are the building blocks in more extensive structures, and the active components in inter‐vesicle functions. A staggered herringbone microfluidic mixer reproducibly gives size‐controlled unilamellar vesicles having low‐permeability bilayer membranes.

Sterically stabilized liposomes production using staggered herringbone micromixer: Effect of lipid composition and PEG-lipid content

“…Despite the high demands for sterically stabilised drug delivery systems, most existing microfluidics studies (not limited to SHM) reported the production of non-PEGylated formulations (Forbes et al, 2019;Guimarães Sá Correia et al, 2017;Kastner et al, 2015;Maeki et al, 2015;Zhigaltsev et al, 2012). Few studies reported the preparation of PEGylated liposomes, which were either very small in size (~50 nm), unstable or of high dispersity (> 0.2) (Dong et al, 2017;Hood et al, 2014;Ran et al, 2016;Zheng and Fyles, 2018;Zhigaltsev et al, 2015;Zizzari et al, 2017). For instance, Zhigaltsev et al failed to produce stable and monodispersed, high phase-transition liposomes (DPPC or HSPC) using SHM microfluidics, and mixing with unsaturated lipids was needed to enhance the stability of these PEGylated liposomes (Zhigaltsev et al, 2015).…”

Microfluidic Nanoparticles for Drug Delivery

“…Different microfluidic approaches have been developed for making liposomes, including the HFF method, microfluidic jetting technique, [ 63 ] droplet emulsion transfer, [ 64 ] electroformation, [ 65 ] NanoAssemblr (Figure 4b), [ 58,66–68 ] tangential flow filtration device, [ 69 ] and other microfluidic devices. [ 70,71 ] Among these methods, the HFF method is a straightforward method that has been widely used to synthesize nanoliposomes with various compositions and functions.…”

“…[61] Also, drug-loaded liposomes produced using microfluidic methods exhibited higher EE, smaller and more uniform size in comparison with those synthesized using the conventional thin-film hydration method. [62] Different microfluidic approaches have been developed for making liposomes, including the HFF method, microfluidic jetting technique, [63] droplet emulsion transfer, [64] electroformation, [65] NanoAssemblr (Figure 4b), [58,[66][67][68] tangential flow filtration device, [69] and other microfluidic devices. [70,71] Among Reproduced with permission.…”