2007 Fiscal Year Final Research Report Summary
Development of Radical Treatment Modality for Curing Allergies and Immune Diseases by a Novel Consept, RTDDS
| Project/Area Number |
18390052
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | University of Shizuoka |
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Principal Investigator |
OKU Naoto University of Shizuoka, School of Pharmaceutical Sciences, Department of Medical Biochemistry, Professor (10167322)
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| Co-Investigator(Kenkyū-buntansha) |
ASAI Tomohiro University of Shizuoka, School of Pharmaceutical Sciences, Department of Medical Biochemistry, Assistant professor (00381731)
SHIMIZU Kosuke University of Shizuoka, School of Pharmaceutical Sciences, Department of Medical Biochemistry, Assistant professor (30423841)
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| Project Period (FY) |
2006 – 2007
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| Keywords | reverse targeting / active targeting / DDS / drug delivery system / liposome / desensitization / allergy / autoimmune disease |
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| Research Abstract |
In this project, we introduce a novel concept of "Reverse Targeting Drug Delivery System, RT-DDS", which is reverse version of DDS, namely, drug carriers would be recognized by target cells. For this purpose, we developed antigen-coupled liposome as one of next-generation liposomes which would be recognized by the antigen-specific immume cells, and named it as" Reverse Targeting Liposome (RT-liposome)". By this liposome, we selectively deliver drugs to the immume cells and damage the cells for the purpose of radical treatment modality of allergies and immune diseases. The results obtained in this study indicated that sensitized immune cells actually targeted inversely to antigen-coupled liposomes. In order to prove the concept of RT-DDS, we selected ovalbumin (OVA) as a model antigen and used OVA-sensitized mouse as an antigen sensitive allergy model. At first, we succeeded to prepare RT-liposomes using OVA, and it was shown that OVA-coupled liposomes were stable in serum. We next observed that OVA-coupled liposomes were recognized by immune cells. We observed that PEGylated OVA-liposome itself induces desensitization against OVA. Although the biodistribution of RT-liposomes in naive or OVA-sensitized mice was not much different, OVA-coupled liposomes highly accumulated in spleen compared to control liposomes, suggesting OVA-conjugation alters the recognition by immune systems. Moreover, it was also shown that OVA-coupled liposomes were co-localized with B cells and accumulated in germinal centers in spleen much earlier than control liposomes. The injection of adriamycin-encapsulated OVA-liposome supressed the production of OVA-specific IgE in OVA-presensitized mice. RT-DDS using adriamycin could be a therapy for IgE induced-allergy. In this study, we demonstrated irrefragability of the concept. RT-DDS could be a new therapeutic strategy for allergy and autoimmune diseases.
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