Biodegradable particles as vaccine delivery systems: size matters.
Poly(lactide-co-glycolide) (PLGA) particles have strong potential as antigen delivery systems. The size of PLGA particles used to vaccinate mice can affect the magnitude of the antigen-specific immune response stimulated. In this study, we fabricated and characterized 17 μm, 7 μm, 1 μm, and 300 nm PLGA particles coloaded with a model antigen ovalbumin (OVA) and CpG oligodeoxynucleotides (CpG ODN). PLGA particles demonstrated a size-dependent burst release followed by a more sustained release of encapsulated molecules. PLGA particles that were 300 nm in size showed the highest internalization by, and maximum activation of, dendritic cells. The systemic antigen-specific immune response to vaccination was measured after administration of two intraperitoneal injections, 7 days apart, of 100 μg OVA and 50 μg CpG ODN in C57BL/6 mice. In vivo studies showed that 300 nm sized PLGA particles generated the highest antigen-specific cytotoxic T cell responses by days 14 and 21. These mice also showed the highest IgG2a:IgG1 ratio of OVA-specific antibodies on day 28. This study suggests that the smaller the PLGA particle used to deliver antigen and adjuvants the stronger the antigen-specific cytotoxic T cell response generated.
Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA.
Vijaya B
VB
Joshi
Sean M
SM
Geary
Aliasger K
AK
Salem
D000818:Animals; D003713:Dendritic Cells / Q000378:metabolism; D016503:Drug Delivery Systems; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D019344:Lactic Acid / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D010047:Ovalbumin / Q000008:administration & dosage; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology
C408982:CPG-oligonucleotide; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D014612:Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010047:Ovalbumin