Development of liposome for targeting therapy against brain tumor

Research Project

Project/Area Number	05671170
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Cerebral neurosurgery
Research Institution	Nagasaki University School of Medicine
Principal Investigator	SHIBATA Shobu Nagasaki University School of Medicine, Professor, 医学部, 教授 (50039517)
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) 山下弘己長崎大学, 医学部, 助手 (30210420)
Project Period (FY)	1993 – 1994
Project Status	Completed (Fiscal Year 1994)
Budget Amount *help	¥2,100,000 (Direct Cost: ¥2,100,000) Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000) Fiscal Year 1993: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywords	Endothelium / Liposome / Cisplatin / 脳腫瘍
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 1.2210^<-4> (cm/sec), and that for 4ﾟC was 0.2110^<-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.