PLGA microspheres for the delivery of a novel subunit TB vaccine

Daniel J Kirby, Ida Rosenkrands, Else M Agger, Peter Andersen, Allan G A Coombes, Yvonne Perrie

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Biodegradable poly(dl-lactide-co-glycolide) microspheres were prepared using a modified double emulsion solvent evaporation method for the delivery of the subunit tuberculosis vaccine (Ag85B-ESAT-6), a fusion protein of the immunodominant antigens 6-kDa early secretory antigenic target (ESAT-6) and antigen 85B (Ag85B). Addition of the cationic lipid dimethyl dioctadecylammonium bromide (DDA) and the immunostimulatory trehalose 6,6'-dibehenate (TDB), either separately or in combination, was investigated for the effect on particle size and distribution, antigen entrapment efficiency, in vitro release profiles and in vivo performance. Optimised formulation parameters yielded microspheres within the desired sub-10 microm range (1.50 +/- 0.13 microm), whilst exhibiting a high antigen entrapment efficiency (95 +/- 1.2%) and prolonged release profiles. Although the microsphere formulations induced a cell-mediated immune response and raised specific antibodies after immunisation, this was inferior to the levels achieved with liposomes composed of the same adjuvants (DDA-TDB), demonstrating that liposomes are more effective vaccine delivery systems compared with microspheres.

LanguageEnglish
Pages282-293
Number of pages12
JournalJournal of Drug Targeting
Volume16
Issue number4
DOIs
Publication statusPublished - 31 May 2008

Fingerprint

Subunit Vaccines
Microspheres
Antigens
Bromides
Liposomes
Tuberculosis Vaccines
Polyglactin 910
Immunodominant Epitopes
Emulsions
Particle Size
Immunization
Vaccines
Lipids
polylactic acid-polyglycolic acid copolymer
Antibodies
Proteins
trehalose 6,6'-dibehenate

Keywords

  • adjuvants, immunologic
  • tuberculosis vaccines
  • chemistry, pharmaceutical
  • drug carriers
  • Drug Delivery Systems
  • emulsions

Cite this

Kirby, D. J., Rosenkrands, I., Agger, E. M., Andersen, P., Coombes, A. G. A., & Perrie, Y. (2008). PLGA microspheres for the delivery of a novel subunit TB vaccine. Journal of Drug Targeting, 16(4), 282-293. https://doi.org/10.1080/10611860801900462
Kirby, Daniel J ; Rosenkrands, Ida ; Agger, Else M ; Andersen, Peter ; Coombes, Allan G A ; Perrie, Yvonne. / PLGA microspheres for the delivery of a novel subunit TB vaccine. In: Journal of Drug Targeting. 2008 ; Vol. 16, No. 4. pp. 282-293.
@article{c4452247698f413caf22b1c6e48a411f,
title = "PLGA microspheres for the delivery of a novel subunit TB vaccine",
abstract = "Biodegradable poly(dl-lactide-co-glycolide) microspheres were prepared using a modified double emulsion solvent evaporation method for the delivery of the subunit tuberculosis vaccine (Ag85B-ESAT-6), a fusion protein of the immunodominant antigens 6-kDa early secretory antigenic target (ESAT-6) and antigen 85B (Ag85B). Addition of the cationic lipid dimethyl dioctadecylammonium bromide (DDA) and the immunostimulatory trehalose 6,6'-dibehenate (TDB), either separately or in combination, was investigated for the effect on particle size and distribution, antigen entrapment efficiency, in vitro release profiles and in vivo performance. Optimised formulation parameters yielded microspheres within the desired sub-10 microm range (1.50 +/- 0.13 microm), whilst exhibiting a high antigen entrapment efficiency (95 +/- 1.2{\%}) and prolonged release profiles. Although the microsphere formulations induced a cell-mediated immune response and raised specific antibodies after immunisation, this was inferior to the levels achieved with liposomes composed of the same adjuvants (DDA-TDB), demonstrating that liposomes are more effective vaccine delivery systems compared with microspheres.",
keywords = "adjuvants, immunologic, tuberculosis vaccines, chemistry, pharmaceutical, drug carriers, Drug Delivery Systems, emulsions",
author = "Kirby, {Daniel J} and Ida Rosenkrands and Agger, {Else M} and Peter Andersen and Coombes, {Allan G A} and Yvonne Perrie",
year = "2008",
month = "5",
day = "31",
doi = "10.1080/10611860801900462",
language = "English",
volume = "16",
pages = "282--293",
journal = "Journal of Drug Targeting",
issn = "1061-186X",
number = "4",

}

Kirby, DJ, Rosenkrands, I, Agger, EM, Andersen, P, Coombes, AGA & Perrie, Y 2008, 'PLGA microspheres for the delivery of a novel subunit TB vaccine' Journal of Drug Targeting, vol. 16, no. 4, pp. 282-293. https://doi.org/10.1080/10611860801900462

PLGA microspheres for the delivery of a novel subunit TB vaccine. / Kirby, Daniel J; Rosenkrands, Ida; Agger, Else M; Andersen, Peter; Coombes, Allan G A; Perrie, Yvonne.

In: Journal of Drug Targeting, Vol. 16, No. 4, 31.05.2008, p. 282-293.

Research output: Contribution to journalArticle

TY - JOUR

T1 - PLGA microspheres for the delivery of a novel subunit TB vaccine

AU - Kirby, Daniel J

AU - Rosenkrands, Ida

AU - Agger, Else M

AU - Andersen, Peter

AU - Coombes, Allan G A

AU - Perrie, Yvonne

PY - 2008/5/31

Y1 - 2008/5/31

N2 - Biodegradable poly(dl-lactide-co-glycolide) microspheres were prepared using a modified double emulsion solvent evaporation method for the delivery of the subunit tuberculosis vaccine (Ag85B-ESAT-6), a fusion protein of the immunodominant antigens 6-kDa early secretory antigenic target (ESAT-6) and antigen 85B (Ag85B). Addition of the cationic lipid dimethyl dioctadecylammonium bromide (DDA) and the immunostimulatory trehalose 6,6'-dibehenate (TDB), either separately or in combination, was investigated for the effect on particle size and distribution, antigen entrapment efficiency, in vitro release profiles and in vivo performance. Optimised formulation parameters yielded microspheres within the desired sub-10 microm range (1.50 +/- 0.13 microm), whilst exhibiting a high antigen entrapment efficiency (95 +/- 1.2%) and prolonged release profiles. Although the microsphere formulations induced a cell-mediated immune response and raised specific antibodies after immunisation, this was inferior to the levels achieved with liposomes composed of the same adjuvants (DDA-TDB), demonstrating that liposomes are more effective vaccine delivery systems compared with microspheres.

AB - Biodegradable poly(dl-lactide-co-glycolide) microspheres were prepared using a modified double emulsion solvent evaporation method for the delivery of the subunit tuberculosis vaccine (Ag85B-ESAT-6), a fusion protein of the immunodominant antigens 6-kDa early secretory antigenic target (ESAT-6) and antigen 85B (Ag85B). Addition of the cationic lipid dimethyl dioctadecylammonium bromide (DDA) and the immunostimulatory trehalose 6,6'-dibehenate (TDB), either separately or in combination, was investigated for the effect on particle size and distribution, antigen entrapment efficiency, in vitro release profiles and in vivo performance. Optimised formulation parameters yielded microspheres within the desired sub-10 microm range (1.50 +/- 0.13 microm), whilst exhibiting a high antigen entrapment efficiency (95 +/- 1.2%) and prolonged release profiles. Although the microsphere formulations induced a cell-mediated immune response and raised specific antibodies after immunisation, this was inferior to the levels achieved with liposomes composed of the same adjuvants (DDA-TDB), demonstrating that liposomes are more effective vaccine delivery systems compared with microspheres.

KW - adjuvants, immunologic

KW - tuberculosis vaccines

KW - chemistry, pharmaceutical

KW - drug carriers

KW - Drug Delivery Systems

KW - emulsions

UR - http://www.tandfonline.com/doi/full/10.1080/10611860801900462

U2 - 10.1080/10611860801900462

DO - 10.1080/10611860801900462

M3 - Article

VL - 16

SP - 282

EP - 293

JO - Journal of Drug Targeting

T2 - Journal of Drug Targeting

JF - Journal of Drug Targeting

SN - 1061-186X

IS - 4

ER -