Formulation and manufacturing of lymphatic targeting liposomes using microfluidics


Authors: S. Khakde, C.B. Roces, A. Cameron, A Devit, 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
  • Blog Posts
Search

Browse by Category

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


related content

Publication - Abstract

High Content Image Analysis Reveals Function of miR-124 Upstream of Vimentin in Regulating Motor Neuron Mitochondria

Tal Yardeni, Raquel Fine, Yuvraj Joshi, Tal Gradus-Pery, Noga Kozer, Irit Reichenstein, Eran Yanowski, Shir Nevo, Hila Weiss-Tishler, Michal Eisenberg-Bord, Tal Shalit, Alexander Plotnikov, Haim M. Barr, Eran Perlson, Eran Hornstein

microRNAs (miRNAs) are critical for neuronal function and their dysregulation is repeatedly observed in neurodegenerative diseases. Here, we implemented high content image analysis for investigating the impact of several miRNAs in mouse primary mot...

Read More


Publication - Summary

Effective Lipidoid Nanoparticle Delivery In Vivo of siRNA Targeting Kappa Light Chain Production in a Murine Xenograft Model

Xun Ma, Ping Zhou, Adin Kugelmass, Denis Toskic, Melissa Warner, Lisa X. Lee, Teresa Fogaren, Ming Wang, Yamin Li, Liu Yang, Qiaobing Xu and Raymond Comenzo

Researchers at Tufts University have recently reported a proof of concept for siRNA-LNP treatment for AL amyloidosis - a bone marrow disorder where Immunoglobulin (Ig) light chains (LC) misfold into amyloids that deposit in a variety of other tissues where they cause disfunction ...
Read More


Stay Informed

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

MENU
X