title: Specific delivery of an immunosuppressive drug to splenic B cells by antigen-modified liposomes and its antiallergic effect.
abstract: Use of the reverse targeting drug delivery system (RT-DDS) is a new targeting strategy based on the specific delivery of drugs to immune cells in antigen-sensitized animals by using antigen-modified liposomes, and it is expected to be a curative treatment for allergic diseases.
  
  
  
  Herein, we prepared ovalbumin (OVA)-modified liposomes encapsulating the immunosuppressive drug FK506 (OVA-LipFK) and aimed to demonstrate the delivery selectivity of the liposomes to splenic B cells, and its antiallergic effect in an OVA-sensitized allergic model mouse.
  
  
  
  Fluorescently labeled OVA-LipFK was intravenously injected into OVA-sensitized mice, and the intrasplenic localization of liposomes was observed. The antiallergic effect of OVA-LipFK in OVA-sensitized mice was examined by measuring the blood levels of OVA-specific IgE and IgG antibodies.
  
  
  
  OVA-LipFK was co-localized to not only B cells but also germinal centers, in the spleen of OVA-sensitized mice. However, there was no accumulation of unmodified liposomes encapsulating FK506 (LipFK) in the splenic B-cell area. In a therapeutic study, OVA-LipFK significantly suppressed the production of both OVA-specific IgE and IgG antibodies in OVA-sensitized mice after the animals had been boosted with OVA, whereas LipFK showed little antiallergic effect.
  
  
  
  The present study suggested that the introduction of RT-DDS for use with immunosuppressive drugs could be useful for the treatment of allergic diseases.
authors.affiliation: a Department of Medical Biochemistry , School of Pharmaceutical Sciences, University of Shizuoka , Yada , Suruga-Ku , Shizuoka , Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: a Department of Medical Biochemistry , School of Pharmaceutical Sciences, University of Shizuoka , Yada , Suruga-Ku , Shizuoka , Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Miyauchi
authors.affiliation: a Department of Medical Biochemistry , School of Pharmaceutical Sciences, University of Shizuoka , Yada , Suruga-Ku , Shizuoka , Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Urakami
authors.affiliation: a Department of Medical Biochemistry , School of Pharmaceutical Sciences, University of Shizuoka , Yada , Suruga-Ku , Shizuoka , Japan.
authors.forename: Kanae
authors.initials: K
authors.lastname: Yamamura-Ichikawa
authors.affiliation: a Department of Medical Biochemistry , School of Pharmaceutical Sciences, University of Shizuoka , Yada , Suruga-Ku , Shizuoka , Japan.
authors.forename: Sei
authors.initials: S
authors.lastname: Yonezawa
authors.affiliation: a Department of Medical Biochemistry , School of Pharmaceutical Sciences, University of Shizuoka , Yada , Suruga-Ku , Shizuoka , Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Asai
authors.affiliation: a Department of Medical Biochemistry , School of Pharmaceutical Sciences, University of Shizuoka , Yada , Suruga-Ku , Shizuoka , Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Oku
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects*; D006967:Hypersensitivity / Q000276:immunology*; D007166:Immunosuppressive Agents; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology*; D013154:Spleen / Q000166:cytology*; D016559:Tacrolimus / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D007166:Immunosuppressive Agents; D008081:Liposomes; D010047:Ovalbumin; D016559:Tacrolimus
keywords: Allergy; B cell; FK506; OVA; RT-DDS; germinal center; liposome