Scale-independent microfluidic production of cationic liposomal adjuvants and development of enhanced lymphatic targeting strategies

Roces, Carla B. and Khadke, Swapnil and Christensen, Dennis and Perrie, Yvonne (2019) Scale-independent microfluidic production of cationic liposomal adjuvants and development of enhanced lymphatic targeting strategies. Molecular Pharmaceutics, 16 (10). pp. 4372-4386. ISSN 1543-8384 (https://doi.org/10.1021/acs.molpharmaceut.9b00730)

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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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