1995 Fiscal Year Final Research Report Summary
Enhanced Efficacy of Immunosuppressant by Modification at Molecular Level
| Project/Area Number |
05671877
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
医薬分子機能学
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| Research Institution | Kyoto Pharmaceutical University |
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Principal Investigator |
TAKADA Kanji Pharmaceutical University Department of Pharmaceutics, Professor, 薬学部, 教授 (30102106)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIKAWA Yukako Kyoto Pharmaceutical University, Department of pharmaceutics, Assistant, 薬学部, 助手 (30278444)
YASUI Hiroshi Kyoto Pharmaceutical Univiersity, Department of pharmaceutics, Assistant, 薬学部, 助手 (20278443)
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| Project Period (FY) |
1993 – 1995
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| Keywords | Cyclospor in A / Immunosuppressant / Molecular level Modification / Liposome / Lymphatic tissue / Bioadhesive |
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| Research Abstract |
The representative immunosuppressants such as cyclosporin A (CyA) and tacrolimus (FK506) have unique pharmacological activities based on the suppression of the activating process of helper T cells by inhibiting the production of interleukin 2 (IL-2). However, the dose-dependent side effects like renal, hepatic and central nerve system are serious clinical problems. As both immunosuppressants are extremely hydrophobic water-insoluble drugs, the available dosage form is limited. Moreover, price of these drugs are very expensive. To solve these problems, there is a need to develop a new dosage form which elucidates immunosuppressive effect with minimum required amount of drug. We prepared several kinds of CyA liposome preparations to deliver CyA to its target organ that contain much lymphatic cells.
From CyA and egg yolk phosphatidylcholine, both liposomes and modified liposomes with bioadhesive polymer, Carbopol, were prepared. From the pharmacokinetic study using rats following iv infusion of test preparations, the distribution of CyA to the liver and the spleen that are rich in lymphatic cells were significantly increased as compared to the CyA solution. Using rat heart transplantation model system, the efficacy of these liposomes preparations were evaluated. Test preparations were injected to transplanted rats 10mg CyA/kg for 7 days and the survival time of the graft was determined.
As compared to the control value, 6.4(]SY.+-.])1.9 day, the mean survival days of liposome and modified liposomes were prolonged to 14.2(]SY.+-.])4.4 and 18.8(]SY.+-.])2.9 days, respectively. These results support the usefulness of targeting CyA to its site of action by physicochemical modification at molecular level.
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