PLGA microspheres for the delivery of a novel subunit TB vaccine.
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.
Kirby
Daniel J
DJ
Medicines Research Unit, School of Life and Health Sciences, Aston University, Birmingham, UK.
Rosenkrands
Ida
I
Agger
Else M
EM
Andersen
Peter
P
Coombes
Allan G A
AG
Perrie
Yvonne
Y
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004655:Emulsions; D005260:Female; D006017:Glycolipids; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D019344:Lactic Acid; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D000644:Quaternary Ammonium Compounds; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000493:pharmacokinetics
D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D004655:Emulsions; D006017:Glycolipids; D007457:Iodine Radioisotopes; D000644:Quaternary Ammonium Compounds; D032581:Tuberculosis Vaccines; C507803:trehalose 6,6'-dibehenate; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C015831:dimethyldioctadecylammonium; D011100:Polyglycolic Acid; D019344:Lactic Acid