1993 Fiscal Year Final Research Report Summary
EXPERIMENTAL AND CLINICAL STUDIES ON DRUG DELIVERY SYSTEM USING ANTI-CANCER AGENTS ENTRAPPED IN LIPOMES
| Project/Area Number |
04670801
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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 |
Digestive surgery
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| Research Institution | Keio University |
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Principal Investigator |
KUMAI Koichiro KEIO UNIVERSITY, SCHOOL OF MEDICENE, ASSISTANT PROFESSOR, 医学部, 専任講師 (30101984)
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| Co-Investigator(Kenkyū-buntansha) |
TADAKUMA Takusi KEIO UNIVERSITY, SCHOOL OF MEDICENE, ASSOCIATE PROFESSOR, 医学部, 助教授 (30051626)
MURAYAMA Yoshihiko KEIO UNIVERSITY, SCHOOL OF MEDICENE, ASSISTANT, 医学部, 助手 (30239553)
SHIBATA Sansei KEIO UNIVERSITY, SCHOOL OF MEDICENE, ASSISTANT, 医学部, 助手 (50216008)
SHIMIZU Hiroyuki KEIO UNIVERSITY, SCHOOL OF MEDICENE, ASSISTANT, 医学部, 助手 (00206210)
HARAHATA Shinobu KEIO UNIVERSITY, SCHOOL OF MEDICENE, ASSISTANT (40189858)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Adriamycin / Liposomes / Monoclonal antibody / Fab' fragment / Ganglioside GM1 / Lymph node metastasis / Endoscopic submucosal injection / temperature sensitive drug delivery system |
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| Research Abstract |
Experimental and clinical studies of three types of drug delivery system (DDS) using adriamycin-containig liposones(Lip-ADM) were conducted. (1) To improve the efficiency of therapeutic effects of Lip-ADM conjugated with monoclonal antibody(Lip-ADM=Ab), Fab' fragment was introduced instead of whole molocule(Lip-ADM=Fab'). An increase in delivery of ADM to the tumor and in inhibition of the tumor growth were observed in the group of mice received Lip-ADM=Feb'. However, the preferencial distribution of Lip-ADM to the reticuloendotherial system(RES) was not much deffernt regardless of using Fab' fragment. In order to reduce the entrapment by RES, ganglioside GM1 or sphingomyerin(SM) were introduced to the component of liposones (stealth Lip-ADM). A decrease in entrapment of ADM in the liver and the spleen was observed in stealth Lip-ADM conjugated with monoclonal aniboy(stealth Lip-ADM=Ab) group. (2) Temperature sensitive liposones (TS-Lip-ADM) were conjugated with mono-clonal antibody(TS-Lip-ADM=Ab). TS-Lip-ADM=Ab consisted of DPPC, DSPC, cholestererol and DTP-DPPE at a molar raio 7 : 2 : 3 : 0.1 maitained temper-ture sensitive release of ADM at 42*C.An increase in delivery of ADM to the rumor and in antitumor effext, combined with 15 min. local rumor hyperthermia 1 hour after drug injection, were observed. (3) As a trget of DDS for lymphatic tissue, a model of lymph node metastasis of gastric tumor was established using VX2 tumor in rabbits. Endoscopic submucosal injection of Lip-ADM(MLV) revealed an increase in deliverty of ADM to the regional lymph node and anti-tumor effect for lymph node metastasis in this model. Clinical application for patients with gastric cancer was performed with similar delivery as expeiment.
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