Manipulation of the surface pegylation in combination with reduced vesicle size of cationic liposomal adjuvants modifies their clearance kinetics from the injection site, and the rate and type of T cell response

Randip Kaur, Vincent W. Bramwell, Daniel J. Kirby, Yvonne Perrie

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26 Citations (Scopus)

Abstract

The mechanism behind the immunostimulatory effect of the cationic liposomal vaccine adjuvant dimethyldioctadecylammonium and trehalose 6,6'-dibehenate (DDA:TDB) has been linked to the ability of these cationic vesicles to promote a depot after administration, with the liposomal adjuvant and the antigen both being retained at the injection site. This can be attributed to their cationic nature, since reduction in vesicle size does not influence their distribution profile yet neutral or anionic liposomes have more rapid clearance rates. Therefore the aim of this study was to investigate the impact of a combination of reduced vesicle size and surface pegylation on the biodistribution and adjuvanticity of the formulations, in a bid to further manipulate the pharmacokinetic profiles of these adjuvants. From the biodistribution studies, it was found that with small unilamellar vesicles (SUVs), 10% PEGylation of the formulation could influence liposome retention at the injection site after 4 days, whilst higher levels (25mol%) of PEG blocked the formation of a depot and promote clearance to the draining lymph nodes. Interestingly, whilst the use of 10% PEG in the small unilamellar vesicles did not block the formation of a depot at the site of injection, it did result in earlier antibody response rates and switch the type of T cell responses from a Th1 to a Th2 bias suggesting that the presence of PEG in the formulation not only control the biodistribution of the vaccine, but also results in different types of interactions with innate immune cells.

LanguageEnglish
Pages331-337
Number of pages7
JournalJournal of Controlled Release
Volume164
Issue number3
DOIs
Publication statusPublished - 28 Dec 2012

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Unilamellar Liposomes
T-Lymphocytes
Liposomes
Injections
Vaccines
Antibody Formation
Pharmacokinetics
Lymph Nodes
Antigens
dimethyldioctadecylammonium
trehalose 6,6'-dibehenate

Keywords

  • liposomes
  • polyethylene glycols
  • DDA
  • TDB
  • vaccine
  • adjuvant
  • dimethyldioctadecylammonium
  • antigen presenting cells
  • trehalose 6,6′-dibehenate

Cite this

@article{764c456101e14c359eac4fd8bfdcfb49,
title = "Manipulation of the surface pegylation in combination with reduced vesicle size of cationic liposomal adjuvants modifies their clearance kinetics from the injection site, and the rate and type of T cell response",
abstract = "The mechanism behind the immunostimulatory effect of the cationic liposomal vaccine adjuvant dimethyldioctadecylammonium and trehalose 6,6'-dibehenate (DDA:TDB) has been linked to the ability of these cationic vesicles to promote a depot after administration, with the liposomal adjuvant and the antigen both being retained at the injection site. This can be attributed to their cationic nature, since reduction in vesicle size does not influence their distribution profile yet neutral or anionic liposomes have more rapid clearance rates. Therefore the aim of this study was to investigate the impact of a combination of reduced vesicle size and surface pegylation on the biodistribution and adjuvanticity of the formulations, in a bid to further manipulate the pharmacokinetic profiles of these adjuvants. From the biodistribution studies, it was found that with small unilamellar vesicles (SUVs), 10{\%} PEGylation of the formulation could influence liposome retention at the injection site after 4 days, whilst higher levels (25mol{\%}) of PEG blocked the formation of a depot and promote clearance to the draining lymph nodes. Interestingly, whilst the use of 10{\%} PEG in the small unilamellar vesicles did not block the formation of a depot at the site of injection, it did result in earlier antibody response rates and switch the type of T cell responses from a Th1 to a Th2 bias suggesting that the presence of PEG in the formulation not only control the biodistribution of the vaccine, but also results in different types of interactions with innate immune cells.",
keywords = "liposomes, polyethylene glycols, DDA, TDB, vaccine, adjuvant, dimethyldioctadecylammonium , antigen presenting cells, trehalose 6,6′-dibehenate",
author = "Randip Kaur and Bramwell, {Vincent W.} and Kirby, {Daniel J.} and Yvonne Perrie",
note = "Copyright {\circledC} 2012 Elsevier B.V. All rights reserved.",
year = "2012",
month = "12",
day = "28",
doi = "10.1016/j.jconrel.2012.07.012",
language = "English",
volume = "164",
pages = "331--337",
journal = "Journal of Controlled Release",
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TY - JOUR

T1 - Manipulation of the surface pegylation in combination with reduced vesicle size of cationic liposomal adjuvants modifies their clearance kinetics from the injection site, and the rate and type of T cell response

AU - Kaur, Randip

AU - Bramwell, Vincent W.

AU - Kirby, Daniel J.

AU - Perrie, Yvonne

N1 - Copyright © 2012 Elsevier B.V. All rights reserved.

PY - 2012/12/28

Y1 - 2012/12/28

N2 - The mechanism behind the immunostimulatory effect of the cationic liposomal vaccine adjuvant dimethyldioctadecylammonium and trehalose 6,6'-dibehenate (DDA:TDB) has been linked to the ability of these cationic vesicles to promote a depot after administration, with the liposomal adjuvant and the antigen both being retained at the injection site. This can be attributed to their cationic nature, since reduction in vesicle size does not influence their distribution profile yet neutral or anionic liposomes have more rapid clearance rates. Therefore the aim of this study was to investigate the impact of a combination of reduced vesicle size and surface pegylation on the biodistribution and adjuvanticity of the formulations, in a bid to further manipulate the pharmacokinetic profiles of these adjuvants. From the biodistribution studies, it was found that with small unilamellar vesicles (SUVs), 10% PEGylation of the formulation could influence liposome retention at the injection site after 4 days, whilst higher levels (25mol%) of PEG blocked the formation of a depot and promote clearance to the draining lymph nodes. Interestingly, whilst the use of 10% PEG in the small unilamellar vesicles did not block the formation of a depot at the site of injection, it did result in earlier antibody response rates and switch the type of T cell responses from a Th1 to a Th2 bias suggesting that the presence of PEG in the formulation not only control the biodistribution of the vaccine, but also results in different types of interactions with innate immune cells.

AB - The mechanism behind the immunostimulatory effect of the cationic liposomal vaccine adjuvant dimethyldioctadecylammonium and trehalose 6,6'-dibehenate (DDA:TDB) has been linked to the ability of these cationic vesicles to promote a depot after administration, with the liposomal adjuvant and the antigen both being retained at the injection site. This can be attributed to their cationic nature, since reduction in vesicle size does not influence their distribution profile yet neutral or anionic liposomes have more rapid clearance rates. Therefore the aim of this study was to investigate the impact of a combination of reduced vesicle size and surface pegylation on the biodistribution and adjuvanticity of the formulations, in a bid to further manipulate the pharmacokinetic profiles of these adjuvants. From the biodistribution studies, it was found that with small unilamellar vesicles (SUVs), 10% PEGylation of the formulation could influence liposome retention at the injection site after 4 days, whilst higher levels (25mol%) of PEG blocked the formation of a depot and promote clearance to the draining lymph nodes. Interestingly, whilst the use of 10% PEG in the small unilamellar vesicles did not block the formation of a depot at the site of injection, it did result in earlier antibody response rates and switch the type of T cell responses from a Th1 to a Th2 bias suggesting that the presence of PEG in the formulation not only control the biodistribution of the vaccine, but also results in different types of interactions with innate immune cells.

KW - liposomes

KW - polyethylene glycols

KW - DDA

KW - TDB

KW - vaccine

KW - adjuvant

KW - dimethyldioctadecylammonium

KW - antigen presenting cells

KW - trehalose 6,6′-dibehenate

U2 - 10.1016/j.jconrel.2012.07.012

DO - 10.1016/j.jconrel.2012.07.012

M3 - Article

VL - 164

SP - 331

EP - 337

JO - Journal of Controlled Release

T2 - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

IS - 3

ER -