PLGA microparticles in respirable sizes enhance an in vitro T cell response to recombinant Mycobacterium tuberculosis antigen TB10.4-Ag85B.
OBJECTIVE
To study the use of poly (lactide-co-glycolide) (PLGA) microparticles in respirable sizes as carriers for recombinant tuberculosis (TB) antigen, TB10.4-Ag85B, with the ultimate goal of pulmonary delivery as vaccine for the prevention of TB.


METHODS
Recombinant TB antigens were purified from E. coli by FPLC and encapsulated into PLGA microparticles by emulsion/spray-drying. Spray-drying condition was optimized by half-factorial design. Microparticles encapsulating TB antigens were assessed for their ability to deliver antigens to macrophages for subsequent presentation by employing an in vitro antigen presentation assay specific to an Ag85B epitope.


RESULTS
Spray-drying condition was optimized to prepare PLGA microparticles suitable for pulmonary delivery (aerodynamic diameter of 3.3 microm). Antigen release from particles exhibited an initial burst release followed by sustained release up to 10 days. Antigens encapsulated into PLGA microparticles induced much stronger interleukin-2 secretion in a T-lymphocyte assay compared to antigen solutions for three particle formulations. Macrophages pulsed with PLGA-MDP-TB10.4-Ag85B demonstrated extended epitope presentation.


CONCLUSIONS
PLGA microparticles in respirable sizes were effective in delivering recombinant TB10.4-Ag85B in an immunologically relevant manner to macrophages. These results set the foundation for further investigation into the potential use of PLGA particles for pulmonary delivery of vaccines to prevent Mycobacterium tuberculosis infection.
Shi
Shuai
S
Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7571, USA.
Hickey
Anthony J
AJ
D000280:Administration, Inhalation; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051379:Mice; D008822:Mice, Transgenic; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000382:microbiology
D000942:Antigens, Bacterial; D011994:Recombinant Proteins; C501710:TB10.4 antigen, Mycobacterium tuberculosis; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid