Design and evaluation of surface and adjuvant modified PLGA microspheres for uptake by dendritic cells to improve vaccine responses

Aiala Salvador; Kerrie J Sandgren; Frank Liang; Elizabeth A Thompson; Richard A Koup; José Luis Pedraz; Rosa Maria Hernandez; Karin Loré; Manoli Igartua

doi:10.1016/j.ijpharm.2015.10.037

Design and evaluation of surface and adjuvant modified PLGA microspheres for uptake by dendritic cells to improve vaccine responses

Int J Pharm. 2015 Dec 30;496(2):371-81. doi: 10.1016/j.ijpharm.2015.10.037. Epub 2015 Oct 22.

Authors

Aiala Salvador¹, Kerrie J Sandgren², Frank Liang³, Elizabeth A Thompson³, Richard A Koup⁴, José Luis Pedraz¹, Rosa Maria Hernandez¹, Karin Loré⁵, Manoli Igartua⁶

Affiliations

¹ 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.
² Clinical Immunology and Allergy unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
³ Clinical Immunology and Allergy unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA.
⁴ Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA.
⁵ 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.
⁶ 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.

PMID: 26475970
DOI: 10.1016/j.ijpharm.2015.10.037

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.

Keywords: Human primary dendritic cells; Monophosphoryl lipid A; PLGA; Polyethyleneimine; Polyinosinic-polycytidilic acid; α-galactosylceramide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic / chemical synthesis
Adjuvants, Immunologic / metabolism*
Animals
Cells, Cultured
Dendritic Cells / metabolism*
Drug Design*
Drug Evaluation, Preclinical / methods
Female
Humans
Lactic Acid / chemical synthesis
Lactic Acid / metabolism*
Mice
Mice, Inbred BALB C
Microspheres*
Polyglycolic Acid / chemical synthesis
Polyglycolic Acid / metabolism*
Polylactic Acid-Polyglycolic Acid Copolymer
Surface Properties
Treatment Outcome
Vaccines / chemical synthesis
Vaccines / metabolism*

Substances

Adjuvants, Immunologic
Vaccines
Polylactic Acid-Polyglycolic Acid Copolymer
Polyglycolic Acid
Lactic Acid