title: Chitosan/sulfated locust bean gum nanoparticles: In vitro and in vivo evaluation towards an application in oral immunization.
abstract: This work proposes the design of nanoparticles based on locus bean gum (LBG) and chitosan to be used as oral immunoadjuvant for vaccination purposes. LBG-based nanoparticles were prepared by mild polyelectrolyte complexation between chitosan (CS) and a synthesized LBG sulfate derivative (LBGS). Morphological characterization suggested that nanoparticles present a solid and compact structure with spherical-like shape. Sizes around 180-200nm and a positive surface charge between +9mV and +14mV were obtained. CS/LBGS nanoparticles did not affect cell viability of Caco-2 cells after 3h and 24h of exposure when tested at concentrations up to 1.0mg/mL. Two model antigens (a particulate acellular extract HE of Salmonella enterica serovar Enteritidis, and ovalbumin as soluble antigen) were associated to CS/LBGS nanoparticles with efficiencies around 26% for ovalbumin and 32% for HE, which resulted in loading capacities up to 12%. The process did not affect the antigenicity of the associated antigens. BALB/c mice were orally immunized with ovalbumin-loaded nanoparticles (100μg), and results indicate an adjuvant effect of the CS/LBGS nanoparticles, eliciting a balanced Th1/Th2 immune response. Thus, CS/LBGS nanoparticles are promising as antigen mucosal delivery strategy, with particular interest for oral administration.
authors.affiliation: CIQA-Centre of Research in Chemistry of Algarve, Faculty of Sciences and Technology, Campus de Gambelas, 8005-139 Faro, Portugal; School of Health-University of Algarve, Avenida Dr. Adelino da Palma Carlos, 8000-510 Faro, Portugal; Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira n.° 228, 4050-313 Porto, Portugal; CBMR-Centre for Biomedical Research, University of Algarve, Faculty of Sciences and Technology, Campus de Gambelas, 8005-139 Faro, Portugal. Electronic address: lvbraz@ualg.pt.
authors.forename: Luis
authors.initials: L
authors.lastname: Braz
authors.affiliation: CBMR-Centre for Biomedical Research, University of Algarve, Faculty of Sciences and Technology, Campus de Gambelas, 8005-139 Faro, Portugal; CCMAR-Centre for Marine Sciences, University of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Grenha
authors.affiliation: UCIBIO, REQUIMTE, Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Domingos
authors.initials: D
authors.lastname: Ferreira
authors.affiliation: CIQA-Centre of Research in Chemistry of Algarve, Faculty of Sciences and Technology, Campus de Gambelas, 8005-139 Faro, Portugal.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Rosa da Costa
authors.affiliation: Department of Microbiology, University of Navarra, 31008 Pamplona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Gamazo
authors.affiliation: i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; INEB, Instituto de Engenharia Biomédica, Biocarrier Group, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal. Electronic address: bruno.sarmento@ineb.up.pt.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000276:immunology; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D005685:Galactans / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007114:Immunization; D008351:Mannans / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D053149:Plant Gums / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D012449:Safety; D013431:Sulfates / Q000737:chemistry*
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D005685:Galactans; D008351:Mannans; D053149:Plant Gums; D013431:Sulfates; D048271:Chitosan; C017471:locust bean gum
keywords: Locust bean gum; Oral immunization; Polymeric nanoparticles