title: Application of galactose-modified liposomes as a potent antigen presenting cell targeted carrier for intranasal immunization.
abstract: The mucosal immune system produces secretory IgA (sIgA) as the first line of defense against invasion by foreign pathogens. Our aim was to develop a galactose-modified liposome as a targeted carrier which can be specifically recognized by macrophage, one of the most important antigen presenting cells. First, galactose was covalently conjugated with 1,2-didodecanoyl-sn-glycero-3-phosphoethanolamine (DLPE) to give a targeted ligand, a galactosyl lipid. The galactosyl lipid was then incorporated into a liposomal bilayer to form a galactosylated liposome carrier. Further, the ovalbumin (OVA) was encapsulated into the galactosylated liposome carriers and mice were intranasally immunized. Confocal laser scanning microscopy and flow cytometry analysis showed that the targeted galactosylated liposome carrier had a higher uptake rate than unmodified liposomes. The targeted galactosylated liposome induced higher levels of tumor necrosis factor-α and interleukin-6 production than unmodified liposomes (P<0.05). Furthermore, 6-week-old BALB/c female mice immunized with the OVA-encapsulated targeted galactosylated liposome had significantly higher OVA-specific s-IgA levels in the nasal and lung wash fluid (P<0.05). In addition, the targeted galactosylated liposome simultaneously augmented the serum IgG antibody response. In summary, the OVA-encapsulated targeted galactosylated liposome induced significantly higher mucosal IgA and systemic IgG antibody titers and is a potential antigen delivery carrier for further clinical applications.
authors.affiliation: School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Hsiao-Wen
authors.initials: HW
authors.lastname: Wang
authors.forename: Ping-Lun
authors.initials: PL
authors.lastname: Jiang
authors.forename: Shen-Fu
authors.initials: SF
authors.lastname: Lin
authors.forename: Hung-Jun
authors.initials: HJ
authors.lastname: Lin
authors.forename: Keng-Liang
authors.initials: KL
authors.lastname: Ou
authors.forename: Win-Ping
authors.initials: WP
authors.lastname: Deng
authors.forename: Lin-Wen
authors.initials: LW
authors.lastname: Lee
authors.forename: Yi-You
authors.initials: YY
authors.lastname: Huang
authors.forename: Pi-Hui
authors.initials: PH
authors.lastname: Liang
authors.forename: Der-Zen
authors.initials: DZ
authors.lastname: Liu
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D005690:Galactose / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D056724:Immunity, Humoral / Q000276:immunology; D018928:Immunity, Mucosal; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D018836:Inflammation Mediators / Q000378:metabolism; D008081:Liposomes / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010714:Phosphatidylethanolamines / Q000737:chemistry
chemical_list: D016207:Cytokines; D004337:Drug Carriers; D005456:Fluorescent Dyes; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D008081:Liposomes; D010714:Phosphatidylethanolamines; D010047:Ovalbumin; D005690:Galactose