1994 Fiscal Year Final Research Report Summary
Development of liposome for targeting therapy against brain tumor
| Project/Area Number |
05671170
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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 |
Cerebral neurosurgery
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| Research Institution | Nagasaki University School of Medicine |
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Principal Investigator |
SHIBATA Shobu Nagasaki University School of Medicine, Professor, 医学部, 教授 (50039517)
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| Co-Investigator(Kenkyū-buntansha) |
SUNAMOTO Junzo Kyoto University, Faculty of Engineering, Professor, 工学部, 教授 (80037811)
TOKUNAGA Yoshiharu Nagasaki University School of Medicine, Assistant Professor, 医学部, 講師 (00207557)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Endothelium / Liposome / Cisplatin |
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| Research Abstract |
Purpose
Liposome encapsulation is an effective method for drug delivery system. In brain, many researches related to liposomes have been reported, but the actual mechanism by which liposome itself permeates through blood-brain barrier (BBB) has not been elucidated. To study the mechanisms, we investigated the BBB permeability of cisplatin (CDDP) encapsulated in liposome using primary culture of bovine brain microvessel endothelial cells (BMEC) as an in vitro BBB model.
Method
BMECs were isolated and cultured on collagen coated polycarbonate membranes according to the protocol of audus and Borchardt. The BMEC confluent monolayrs with polycarbonate membranes were detached from the dishes, and placed in between the two halves of side-by-side diffusion cells. Each chamber was filled with 3ml of transport assay buffer, and kept at 37ﾟC of 4ﾟC.Liposomes encapsulating CDDP were prepared from egg-phosphatidylcholine by reverse-phase evaporation method. The donor chamber was pulsed with liposome encapsulating CDDP suspension or free CDDP solution to a final concentration of 20muM.The receptor chamber was sampled at 15-, 30-min intervals. The platinum concentration was measured by atomic absorption spectrophotometer.
Result adn Conclusion
At 30-min, the permeability coefficient of liposomal CDDP at 37ﾟC was 1.22*10^<-4> (cm/sec), and that for 4ﾟC was 0.21*10^<-4> (cm/sec) which is statistically significant. Our findings suggest that CDDP encapsulated in liposome could transported through BBB by way of energy-dependent transcellular transport.
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