title: Alginate coated chitosan nanoparticles are an effective subcutaneous adjuvant for hepatitis B surface antigen.
abstract: We recently described a delivery system that is composed of a chitosan core to which the hepatitis B surface antigen (HBsAg) was adsorbed and subsequently coated with sodium alginate. In this present work, alginate coated chitosan nanoparticles were evaluated as a subcutaneous adjuvant for HBsAg. HBsAg loaded, alginate coated or uncoated chitosan nanoparticles, associated or not with CpGODN were subcutaneously administered to mice and several immunological parameters were evaluated. A high anti-HBsAg IgG titer (2271+/-120 mIU/ml), with the majority of antibodies being of Th2 type, was observed within group I, vaccinated with HBsAg loaded onto coated nanoparticles. However, regarding cellular immune response, no significant differences were observed for antigen-specific splenocyte proliferation or for the secretion of IFN-gamma and IL-4, when compared to the control group. The co-delivery of antigen-loaded nanoparticles in the presence of the immunopotentiator, CpG ODN 1826, resulted in an increase of anti-HBsAg IgG titers that was not statistically different from the first group; however, an increase of the IgG2a/IgG1 ratio from 0.1 to 1.0 and an increase (p<0.01) of the IFN-gamma production by the splenocytes stimulated with the HBV antigen was observed. The enhancement of the immune response observed with the antigen-loaded nanoparticles demonstrated that chitosan is a promising platform for parenteral HBsAg delivery and, when co-administered with the CpG ODN, resulted in a mixed Th1/Th2 type immune response.
authors.affiliation: Center for Pharmaceutical Studies, Faculty of Pharmacy, University of Coimbra, 3000-295 Coimbra, Portugal. olga@ci.uc.pt
authors.forename: Olga
authors.initials: O
authors.lastname: Borges
authors.forename: Marta
authors.initials: M
authors.lastname: Silva
authors.forename: Adriano
authors.initials: A
authors.lastname: de Sousa
authors.forename: Gerrit
authors.initials: G
authors.lastname: Borchard
authors.forename: Hans E
authors.initials: HE
authors.lastname: Junginger
authors.forename: Anabela
authors.initials: A
authors.lastname: Cordeiro-da-Silva
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry; D000464:Alginates / Q000737:chemistry; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001672:Biocompatible Materials / Q000008:administration & dosage; D002478:Cells, Cultured; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D004247:DNA / Q000276:immunology; D016503:Drug Delivery Systems; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage* / Q000276:immunology; D006603:Hexuronic Acids / Q000737:chemistry; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009838:Oligodeoxyribonucleotides; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000464:Alginates; D000914:Antibodies, Viral; D001672:Biocompatible Materials; C423449:CpG ODN 1826; D006514:Hepatitis B Surface Antigens; D006603:Hexuronic Acids; D008934:Mitogens; D009838:Oligodeoxyribonucleotides; D014761:Viral Hepatitis Vaccines; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D020723:Glucuronic Acid; D004247:DNA; D048271:Chitosan