title: Protamine-based nanoparticles as new antigen delivery systems.
abstract: The use of biodegradable nanoparticles as antigen delivery vehicles is an attractive approach to overcome the problems associated with the use of Alum-based classical adjuvants. Herein we report, the design and development of protamine-based nanoparticles as novel antigen delivery systems, using recombinant hepatitis B surface antigen as a model viral antigen. The nanoparticles, composed of protamine and a polysaccharide (hyaluronic acid or alginate), were obtained using a mild ionic cross-linking technique. The size and surface charge of the nanoparticles could be modulated by adjusting the ratio of the components. Prototypes with optimal physicochemical characteristics and satisfactory colloidal stability were selected for the assessment of their antigen loading capacity, antigen stability during storage and in vitro and in vivo proof-of-concept studies. In vitro studies showed that antigen-loaded nanoparticles induced the secretion of cytokines by macrophages more efficiently than the antigen in solution, thus indicating a potential adjuvant effect of the nanoparticles. Finally, in vivo studies showed the capacity of these systems to trigger efficient immune responses against the hepatitis B antigen following intramuscular administration, suggesting the potential interest of protamine-polysaccharide nanoparticles as antigen delivery systems.
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Health Research Institute of Santiago de Compostela (IDIS), Dept. of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Univ. of Santiago de Compostela, Santiago de Compostela, Spain; Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago, Chile. Electronic address: jvgonzal@uc.cl.
authors.forename: José Vicente
authors.initials: JV
authors.lastname: González-Aramundiz
authors.affiliation: Immunology, Biomedical Research Center (CINBIO) and Institute of Biomedical Research of Vigo (IBIV), Universidad de Vigo, Campus Lagoas Marcosende, Vigo, Pontevedra, Spain. Electronic address: mpeleteiro@uvigo.es.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Peleteiro Olmedo
authors.affiliation: Immunology, Biomedical Research Center (CINBIO) and Institute of Biomedical Research of Vigo (IBIV), Universidad de Vigo, Campus Lagoas Marcosende, Vigo, Pontevedra, Spain. Electronic address: africa@uvigo.es.
authors.forename: África
authors.initials: Á
authors.lastname: González-Fernández
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Health Research Institute of Santiago de Compostela (IDIS), Dept. of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Univ. of Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: mariaj.alonso@usc.es.
authors.forename: María José
authors.initials: MJ
authors.lastname: Alonso Fernández
authors.affiliation: Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Health Research Institute of Santiago de Compostela (IDIS), Dept. of Pharmacy and Pharmaceutical Technology, School of Pharmacy, Univ. of Santiago de Compostela, Santiago de Compostela, Spain. Electronic address: noemi.csaba@usc.es.
authors.forename: Noemi Stefánia
authors.initials: NS
authors.lastname: Csaba
mesh_terms: D000464:Alginates / Q000737:chemistry; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016207:Cytokines / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004355:Drug Stability; D004356:Drug Storage; D020723:Glucuronic Acid / Q000737:chemistry; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage* / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology; D006603:Hexuronic Acids / Q000737:chemistry; D006820:Hyaluronic Acid / Q000737:chemistry; D008264:Macrophages / Q000276:immunology; D053758:Nanoparticles; D010316:Particle Size; D011479:Protamines / Q000737:chemistry*
chemical_list: D000464:Alginates; D000941:Antigens; D016207:Cytokines; D004337:Drug Carriers; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D006603:Hexuronic Acids; D011479:Protamines; D020723:Glucuronic Acid; D006820:Hyaluronic Acid
keywords: Antigen delivery; Hepatitis B; Hyaluronic acid; Hyaluronic acid (PubChem CID: 3084050); Nanoparticles; Protamine; Protamine sulfate (PubChem SID: 7849283); Sodium alginate (PubChem SID: 496141); Vaccine