title: Application of Magnesium Pyrophosphate-Based Sponge-Like Microparticles to Enhance the Delivery Efficiency and Adjuvant Effects of Polyriboinosinic-Polyribocytidylic Acid in Immune Cells.
abstract: The magnesium pyrophosphate particle (MgPP) is a unique and safe carrier that is prepared by simply mixing magnesium chloride and sodium pyrophosphate. In this study, we investigated whether MgPP can be used to deliver nucleic acid-based adjuvants to immune cells. Polyriboinosinic-polyribocytidylic acid (polyI:C), a ligand for toll-like receptor 3, was selected as a model nucleic acid-based adjuvant. PolyI:C-loaded MgPP (polyI:C-MgPP) was prepared by adding polyI:C during the MgPP preparation process. Efficient loading of polyI:C into MgPP was confirmed by measuring the absorbance at 260 nm after disruption of polyI:C-MgPP by ethylenediaminetetraacetic acid. Scanning electron microscopy revealed that both MgPP and polyI:C-MgPP had a unique sponge-like shape with a diameter of approximately 1 μm. PolyI:C-MgPP was more efficiently taken up by toll-like receptor 3-positive RAW264.7 cells than naked polyI:C, and its uptake stimulated increased tumor necrosis factor-α production. When the presentation of ovalbumin (OVA), a model antigen, was evaluated after the addition of OVA along with naked polyI:C or polyI:C-MgPP to mouse dendritic DC2.4 cells, polyI:C-MgPP substantially increased OVA presentation. These results indicate that MgPP is a useful delivery vehicle for polyI:C and that polyI:C-MgPP is an effective immune cell adjuvant.
authors: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Shoichi
authors: S
authors: Takagi
authors: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Yuki
authors: Y
authors: Takahashi
authors: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Kanako
authors: K
authors: Sugimura
authors: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors: Makiya
authors: M
authors: Nishikawa
authors: Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: takakura@pharm.kyoto-u.ac.jp.
authors: Yoshinobu
authors: Y
authors: Takakura
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D011756:Diphosphates / Q000008:administration & dosage* / Q000378:metabolism; D017616:Magnesium Compounds / Q000008:administration & dosage* / Q000378:metabolism; D051379:Mice; D008863:Microspheres; D011070:Poly I-C; D011119:Polynucleotides / Q000008:administration & dosage* / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D011756:Diphosphates; D017616:Magnesium Compounds; D011119:Polynucleotides; D051196:Toll-Like Receptor 3; C034732:magnesium pyrophosphate; D011070:Poly I-C
keywords: immunology; microspheres; vaccine adjuvants