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

Carla B. Roces, Swapnil Khadke, Dennis Christensen, Yvonne Perrie

Research output: Contribution to journalArticle

12 Citations (Scopus)
23 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)4372-4386
Number of pages15
JournalMolecular Pharmaceutics
Volume16
Issue number10
Early online date22 Aug 2019
DOIs
Publication statusPublished - 7 Oct 2019

Keywords

  • microfluidics
  • manufacture
  • vaccine adjuvants
  • cationic liposomes
  • lymphatic targeting

Cite this