title: Interactions of poly (anhydride) nanoparticles with macrophages in light of their vaccine adjuvant properties.
abstract: Understanding how nanoparticles are formed and how those processes ultimately determine the nanoparticles' properties and their impact on their capture by immune cells is key in vaccination studies. Accordingly, we wanted to evaluate how the previously described poly (anhydride)-based nanoparticles of the copolymer of methyl vinyl ether and maleic anhydride (NP) interact with macrophages, and how this process depends on the physicochemical properties derived from the method of preparation. First, we studied the influence of the desolvation and drying processes used to obtain the nanoparticles. NP prepared by the desolvation of the polymers in acetone with a mixture of ethanol and water yielded higher mean diameters than those obtained in the presence of water (250nm vs. 180nm). In addition, nanoparticles dried by lyophilization presented higher negative zeta potentials than those dried by spray-drying (-47mV vs. -35mV). Second, the influence of the NP formulation on the phagocytosis by J774 murine macrophage-like cell line was investigated. The data indicated that NPs prepared in the presence of water were at least three-times more efficiently internalized by cells than NPs prepared with the mixture of ethanol and water. Besides, lyophilized nanoparticles appeared to be more efficiently taken up by J744 cells than those dried by spray-drying. To further understand the specific mechanisms involved in the cellular internalization of NPs, different pharmacological inhibitors were used to interfere with specific uptake pathways. Results suggest that the NP formulations, particularly, nanoparticles prepared by the addition of ethanol:water, are internalized by the clathrin-mediated endocytosis, rather than caveolae-mediated mechanisms, supporting their previously described vaccine adjuvant properties.
authors.affiliation: Department of Microbiology, University of Navarra, 31008 Pamplona, Spain. Electronic address: cgamazo@unav.es.
authors.forename: C
authors.initials: C
authors.lastname: Gamazo
authors.affiliation: Department of Pharmacy, University of Bonn, 53115 Bonn, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Bussmann
authors.affiliation: Department of Pharmacy, University of Bonn, 53115 Bonn, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Giemsa
authors.affiliation: Department of Microbiology, University of Navarra, 31008 Pamplona, Spain.
authors.forename: A I
authors.initials: AI
authors.lastname: Camacho
authors.affiliation: Departament of Chemistry, Universidad Nacional de Ingeniería, Lima 25, Lima, Perú
authors.forename: Daisy
authors.initials: D
authors.lastname: Unsihuay
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, University of Navarra, 31008 Pamplona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Martín-Arbella
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, University of Navarra, 31008 Pamplona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Irache
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D008264:Macrophages / Q000502:physiology*; D008298:Maleates / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D053758:Nanoparticles; D010587:Phagocytosis / Q000187:drug effects; D011095:Polyethylenes / Q000378:metabolism / Q000494:pharmacology*; D014612:Vaccines / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D008298:Maleates; D011095:Polyethylenes; D014612:Vaccines; C043105:poly(methyl vinyl ether-co-maleic anhydride)
keywords: Antigen presenting cell; Cellular uptake; Clathrin; Macrophage; Nanoparticle