title: Design and evaluation of surface and adjuvant modified PLGA microspheres for uptake by dendritic cells to improve vaccine responses.
abstract: Designing strategies for targeting antigens to dendritic cells is a major goal in vaccinology. Here, PLGA (poly lactic-co-glycolic acid) microspheres and with several surface modifications that affect to their uptake by human blood primary dendritic cells and monocytes have been evaluated. Higher uptake was found by all the cell types when cationic microspheres (PLGA modified with polyethylene imine) were used. These cationic particles were in vivo evaluated in mice. In addition, MPLA(1) or poly(I:C)(2) and α-GalCer(3) were also encapsulated to address their adjuvant effect. All the microspheres were able to produce humoral immune responses, albeit they were higher for cationic microspheres. Moreover, surface charge seemed to have a role on biasing the immune response; cationic microspheres induced higher IFN-γ levels, indicative of Th1 activation, while unmodified ones mainly triggered IL4 and IL17A release, showing Th2 activation. Thus, we have shown here the potential and versatility of these MS, which may be tailored to needs.
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain.
authors.forename: Aiala
authors.initials: A
authors.lastname: Salvador
authors.affiliation: Clinical Immunology and Allergy unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Kerrie J
authors.initials: KJ
authors.lastname: Sandgren
authors.affiliation: Clinical Immunology and Allergy unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Liang
authors.affiliation: Clinical Immunology and Allergy unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Thompson
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Pedraz
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Hernandez
authors.affiliation: Clinical Immunology and Allergy unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA. Electronic address: karin.lore@ki.se.
authors.forename: Karin
authors.initials: K
authors.lastname: Loré
authors.affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain. Electronic address: manoli.igartua@ehu.es.
authors.forename: Manoli
authors.initials: M
authors.lastname: Igartua
mesh_terms: D000276:Adjuvants, Immunologic / Q000138:chemical synthesis / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000138:chemical synthesis / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D011100:Polyglycolic Acid / Q000138:chemical synthesis / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013499:Surface Properties; D016896:Treatment Outcome; D014612:Vaccines / Q000138:chemical synthesis / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; D014612:Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Human primary dendritic cells; Monophosphoryl lipid A; PLGA; Polyethyleneimine; Polyinosinic-polycytidilic acid; α-galactosylceramide