The Preparation of Cationic Liposome-Based Vaccine Adjuvant by Microfluidics Method

Microfluidics is a reliable and promising method for preparing the large-scale particle-based pharmaceutics. It can be expanded from research laboratory to good manufacturing practice production for clinical experiments and commercial pharmaceuticals. One of the useful characteristics of microfluidics is its ability to control various parameters. The researchers monitored the parameters of the microfluidics preparation of a cationic liposome-based vaccine adjuvant CAF09b.

CAF09b, a cationic liposome-based adjuvant, is composed of dioctadcyldimethylammonium bromide (DDA), monomycoloyl glycerol analogue 1 (MMG) and polyinosinic:polycytidilic [poly(I:C)]. It has been assessed in therapeutic cancer vaccines. Currently, the manufacturing method of the adjuvant is a top-down approach with bulk lipid hydration and high shear mixing. The method regulates the sizes of liposomal particles through the input of energy resulting from the force from high shear mixing. Microfluidics utilizes a different method to prepare liposomes by mixing lipid components and using lamellar mixing. Some of the variables can be precisely controlled in this method, including total flow rate (TFR), flow rate ratio (FRR), aqueous buffer, organic solvent and lipid concentration. The method can also be used to prepare other nanoparticles with different morphologies. For instance, during the liposome formation, complexing nucleic acids produce lipid nanoparticles rather than liposomes.

In order to achieve satisfactory particle size and colloidal stability physicochemical properties, the researchers successfully transferred the production of CAF09b from a slow, complex and multi-stage process to a microfluidic-based and single-step liposome synthesis process. Through the experiments, they found that particle sizes were dependent on flow rate ratio, and colloidal stability was dependent on the concentration of lipid and organic solvent. The important thing is that the zeta potential and adsorption rates for poly(I:C) were not changed by changing the preparing method. The study demonstrates some characteristics of microfluidics-based production of liposomes and other lipid-based nanoparticles that make it so appealing in large-scale manufacturing.

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