title: Suppression of immune response by antigen-modified liposomes encapsulating model agents: a novel strategy for the treatment of allergy.
abstract: A specific antigen-sensitized animal has antigen-specific immune cells that recognize the antigen. Therefore, an antigen-modified drug carrier would be recognized by the immune cells. When such a carrier encapsulates certain drugs, these drugs should be specifically delivered to the immune cells. To examine this strategy, ovalbumin (OVA) was used as model antigen, and mice were presensitized with 100 μg of OVA with Alum. For preparing OVA-modified liposomes (OVA-lipo), OVA was incubated with DSPE-PEG-NHS and resulting DSPE-PEG-OVA was inserted into liposomes. OVA-specific IgG was produced 6-fold higher by intravenous injection of OVA-lipo thrice (10 μg as OVA in each injection) in OVA-sensitized mice, than that by the injection of control liposomes, suggesting that OVA-lipo was recognized by the antigen-specific immune cells. Moreover, intra-splenic accumulation of OVA-lipo was observed in OVA-sensitized mice, but not in naive mice. To achieve the delivery of a drug to specific immune cells, OVA-lipo encapsulated low dose of doxorubicin (DOX) as a model drug (20 μg DOX/mouse, Ca. 1 mg/kg) was injected in the sensitized mice. The injection of OVA-lipo encapsulating DOX suppressed the production of IgE against OVA, suggesting that the specific delivery of the drug to immune cells responsible for OVA recognition was achieved and that these immune cells were removed by the drug treatment. This strategy would be useful for the fundamental treatment of allergy by the use of immunosuppressing agents.
authors: Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka 52-1 Yada, Suruga-ku, Shizuoka, Shizuoka 422-8526, Japan.
authors: Kanae
authors: K
authors: Ichikawa
authors: Tomohiro
authors: T
authors: Asai
authors: Kosuke
authors: K
authors: Shimizu
authors: Sei
authors: S
authors: Yonezawa
authors: Takeo
authors: T
authors: Urakami
authors: Haruna
authors: H
authors: Miyauchi
authors: Hiroto
authors: H
authors: Kawashima
authors: Tatsuhiro
authors: T
authors: Ishida
authors: Hiroshi
authors: H
authors: Kiwada
authors: Naoto
authors: N
authors: Oku
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D000941:Antigens / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D006967:Hypersensitivity / Q000628:therapy; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007668:Kidney / Q000378:metabolism; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D013154:Spleen / Q000378:metabolism
chemical_list: C512968:1,2-dioleoyl-3-phosphoethanolamine-n-(poly(ethyleneglycol))-hydroxy succinamide; D000903:Antibiotics, Antineoplastic; D000941:Antigens; D007074:Immunoglobulin G; D008081:Liposomes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D007073:Immunoglobulin E; D011092:Polyethylene Glycols; D004317:Doxorubicin; D010047:Ovalbumin; D002784:Cholesterol; C010942:1,2-distearoyllecithin