Scale-Independent Microfluidic Production of Cationic Liposomal Adjuvants and Development of Enhanced Lymphatic Targeting Strategies


Authors: C.B. Roces, S. Khadke, D. Christensen and Y. Perrie

Journal: Molecular Pharmaceutics

DOI: 10.1021/acs.molpharmaceut.9b00730

Publication - Abstract

August 19, 2019

Abstract

Cationic liposomes prepared from dimethyldioctadecylammonium bromide (DDAB) and trehalose 6,6′-dibehenate (TDB) are strong liposomal adjuvants. As with many liposome formulations, within the laboratory DDAB:TDB is commonly prepared by the thin-film method, which is difficult to scale-up and gives high batch-to-batch variability. In contrast, controllable technologies such as microfluidics offer robust, continuous, and scale-independent production. Therefore, within this study, we have developed a microfluidic production method for cationic liposomal adjuvants that is scale-independent and produces liposomal adjuvants with analogous biodistribution and immunogenicity compared to those produced by the small-scale lipid hydration method. Subsequently, we further developed the DDAB:TDB adjuvant system to include a lymphatic targeting strategy using microfluidics. By exploiting a biotin–avidin complexation strategy, we were able to manipulate the pharmacokinetic profile and enhance targeting and retention of DDAB:TDB and antigen within the lymph nodes. Interestingly, redirecting these cationic liposomal adjuvants did not translate into notably improved vaccine efficacy.

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