Precision Transition of Bicelle to Liposome as Carriers of a Hydrophilic Biologically Active Compound by Microfluidic Mixing Integrated Micro-structure

Although a microfluidic technique for vesicle synthesis has drawn attention in the biomedical field due to its superiority in size control and monodispersity, it has suffered from the extraction of residual solvent. Previous studies attempted the solvent-free microfluidic method using the bicelle-to-vesicle transition, but only a limited size of vesicles was obtained with low membrane properties on account of inefficient mixing. In this paper, we suggest the solvent-free and non-stimulus method for the vesicle preparation using a microfluidic chip with different types of mixing structures, among which the tilted-type structure performed an efficient mixing. With this micromixer, lipid vesicles can be continuously obtained at high yields by diluting bicelle solutions composed of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) and DHPC (1,2-dihexanoyl-sn-glycero-3-phosphocholine). After passing through the microfluidic chip, DMPC bilayer domain coalesced and formed vesicle, while DHPC could dissolve into an aqueous phase. The membrane properties of the vesicles exhibited a highly ordered phase, indicating that DHPCs were removed from transitioned vesicles after dilution in a microfluidic chip. Moreover, by controlling the dilution ratio, vesicles of various sizes ranging from 90 to 480 nm with an enhanced monodispersity can be obtained without any additional process.