Formulation and manufacturing of lymphatic targeting liposomes using microfluidics


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 investigated. 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 result form preferential uptake by macrophages. In terms of vesicle size, smaller unilamellar vesicles gave high lymphatic targeting and a 10-fold increase in concentration was achieved in dose escalation studies. Given that effective trafficking to the lymphatics was achieved, the next step was to enhance retention of the liposomes within the lymphatics, therefore the 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, the 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 (~90nm) 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.

Publication DOI:
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: © 2019, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Funding: EU Horizon 2020 project TBVAC 2020 (Grant no. 643381).
Uncontrolled Keywords: Avidin,Biotin,Liposomes,Lymphatic targeting,Microfluidics,Protein delivery,Vaccines,Pharmaceutical Science
Publication ISSN: 1873-4995
Last Modified: 01 Nov 2023 08:11
Date Deposited: 19 Aug 2019 09:40
Full Text Link:
Related URLs: https://linking ... 168365919303128 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2019-08-10
Published Online Date: 2019-06-03
Accepted Date: 2019-06-01
Authors: Khadke, Swapnil
Roces, Carla B.
Cameron, Allan
Devitt, Andrew (ORCID Profile 0000-0002-4651-6761)
Perrie, Yvonne

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