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.

Advanced Search

close
  • Publications
  • Application Notes
  • Posters
  • Workshops
  • Videos & Webinars
  • Articles
Search

Browse by Category

  • Application
    • Diagnostic and Imaging
    • Genetic Medicine
    • Hematology
    • Metabolic Disorders
    • Neuroscience
    • Oncology
    • Skeletal Disorders
    • Targeted Drug Delivery
    • Vaccines
    • Other Applications
    • Cell therapy
  • Formulation
    • Liposomes
    • Nucleic Acid Lipid Nanoparticles
    • Polymeric Nanoparticles
    • Other Formulations
  • Payload
    • DNA
    • microRNA
    • mRNA
    • siRNA
    • Small Molecule Drugs
    • Other Payloads


related content

Publication - Abstract

Microsystems offer promising possibilities to produce nanoparticles which can be used as carriers for poorly water-soluble active substances. The aim of the present study was to compare the preparation of lipid nanoparticles by precipitation in different microsystems: A segmented...
Read More


Publication - Abstract

Rational Design of Adjuvants for Subunit Vaccines: The Format of Cationic Adjuvants Affects the Induction of Antigen-specific Antibody Responses

G. Anderluzzi, S.T. Schmidt, R. Cunliffe, S. Woods, C.W. Roberts, D. Veggi, I. Ferlenghi, D.T. O'Hagan, B.C. Baudner and Y. Perrie

Read More


Sign Up and Stay Informed
Sign up today to automatically receive new Cytiva, formerly Precision NanoSystems application notes, conference posters, relevant science publications, and webinar invites.