Co-delivery of polyinosinic:polycytidylic acid and flagellin by poly(lactic- co -glycolic acid) MPs synergistically enhances immune response elicited by intranasally delivered hepatitis B surface antigen

• Published in: International journal of nanomedicine 2017-01, Vol.12, p.6617-6632
• Main Authors: Dai, Xiaojing, He, Jintian, Zhang, Ruxia, Wu, Guanghao, Xiong, Fangfang, Zhao, Baohua
• Format: Article
• Language: English
• Subjects: Acids; Administration, Intranasal; Analysis; Animals; Antigens; Biomedical materials; Chitosan - chemistry; Dendritic cells; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Synergism; Female; flagellin; Flagellin - administration & dosage; Hepatitis; Hepatitis B; hepatitis B surface antigen; Hepatitis B Surface Antigens - administration & dosage; Immune response; Influenza; Interferon-gamma - metabolism; Interleukin-10 - metabolism; Interleukin-12 - metabolism; Intranasal vaccination; Lactic Acid - chemistry; Ligands; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Microspheres; Nanoparticles; Nose; Original Research; Peptides; PLGA microparticles; Poly I-C - administration & dosage; Polyglycolic Acid - chemistry; polyinosinic:polycytidylic acid; Proteins; Rats, Sprague-Dawley; Toll-like receptor; Toll-like receptors
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S146912

The aim of the present work was to investigate the synergistic effect between toll-like receptor (TLR) 3 ligand polyinosinic:polycytidylic acid (pI:C) and TLR5 ligand flagellin (FLN) on immune responses induced by nasally delivered hepatitis B virus surface antigen (HBsAg). Mannan and chitosan oligosaccharide-modified, pH-responsive poly(lactic- -glycolic acid) (MC-PLGA) microparticles (MPs) containing HBsAg, FLN, pI:C or both ligands were prepared with a double-emulsion method. In vitro uptake experiments show that cellular uptake of MC-PLGA MPs by macrophages was through energy-dependent, receptor-mediated endocytosis mechanism. After uptake of MPs by macrophages, MC-PLGA MPs existed both in the endo-some and in the cytoplasm. FLN and pI:C in solution or MP formulation could synergize to activate macrophages and induce higher pro-inflammatory cytokines interleukin (IL)-6, IL-12, interferon-γ and anti-inflammatory cytokines IL-10 compared to single TLR ligand (