Formulation and Manufacturing of Lymphatic Targeting Liposomes Using Microfluidics


Authors: S. Khakde, C.B. Roces, A. Cameron, A Devit and Y. Perrie

Journal: Journal of Controlled Release

DOI: 10.1016/j.jconrel.2019.06.002

Publication - Abstract

June 03, 2019

Abstract

The lymphatics are a target for a range of therapeutic purposes, including cancer therapy and vaccination and both vesicle size and charge have been considered as factors controlling lymphatic targeting. Within this work, a range of liposomal formulations were investigated to develop a liposomal lymphatic targeting system. Initial screening of formulations considered the effect of charge, with neutral, cationic and anionic liposomes being considered. Biodistribution studies demonstrated that after intramuscular injection, anionic liposomes offered the most rapid clearance to the draining lymphatics with cationic liposomes forming a depot at the injection site. Anionic liposomes containing phosphatidylserine showed higher clearance to the lymphatics and this may be a results of preferential uptake by macrophages. In terms of vesicle size, smaller unilamellar vesicles gave high lymphatic targeting and 10-fold increases in concentration were achieved in dose escalation studies (up to 40 mg of lipids). Given that effective trafficking to the lymphatics was achieved, the next step was to enhance retention of the liposomes within the lymphatics, therefore this liposome formulation was combined with an avidin/biotin complex mechanism. The affinity of avidin for biotin allows biotinylated liposomes to complex in the presence of avidin. By pre-dosing with avidin, this biotin-avidin complex can be exploited to promote longer retention of the liposomes at the draining lymphatics. To load these small, biotinylated liposomes with protein, microfluidics manufacturing was used. Using microfluidics, protein could easily be incorporated in these small (~90 nm) biotinylated liposomes. Both liposome and protein retention at the local draining lymph nodes was demonstrated with the liposome-biotin-avidin system. These results demonstrate that microfluidics can be used to prepare protein-loaded liposomes that offer enhanced lymphatic targeting and retention of both the liposomes and entrapped antigen.

 
 

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

Lipid Nanoparticle Formulation Increases Efficiency of DNA-Vectored Vaccines/Immunoprophylaxis in Animals Including Transchromosomic Bovines

E.M. Mucker, P.P. Karmali, J. Vega, S.A. Kwilas, H. Wu, M. Joselyn, J. Ballantyne, D. Sampey, R. Mukthavaram, E. Sullivan, P. Chivukula and J.W. Hooper

The use of nucleic acid as a drug substance for vaccines and other gene-based medicines continues to evolve. Here, we have used a technology originally developed for mRNA in vivo delivery to enhance the immunogenicity of DNA vaccines. We demonstrate that neutralizing antibodies p...
Read More


Publication - Abstract

Read More


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