title: Preparation of poly-lactic acid microspheres containing the angiogenesis inhibitor TNP-470 with medium-chain triglyceride and the in vitro evaluation of release profiles.
abstract: TNP-470 (AGM-1470, 6-0-(N-chloroacetylcarbamoyl)-fumagillol), a derivative of fumagillin, is a promising angiogenesis inhibitor. However, as TNP-470 is very unstable in in vitro and in vivo, it has been difficult to verify its pharmacological efficacy in the clinical medicine. The preparation of a drug delivery system (DDS) in a microsphere form was studied for the stable inclusion and controlled release of TNP-470. Medium-chain triglyceride (MCTG) as an effective stabilizer and poly-lactic acid (PLA) as a biodegradable carrier were used for this purpose. The release of TNP-470 from the MCTG containing DDS continued for approximately 2 weeks, while the release of TNP-470 from the one without MCTG stopped after only 5 days. It was proved that TNP-470 could be released much more stable for much longer period from the MCTG containing DDS compared to the one without DDS.
authors.affiliation: Interdisciplinary Graduate School of Science and Technology, Kinki University, Osaka, Japan.
authors.forename: Sachiro
authors.initials: S
authors.lastname: Kakinoki
authors.forename: Chikao
authors.initials: C
authors.lastname: Yasuda
authors.forename: Isao
authors.initials: I
authors.lastname: Kaetsu
authors.forename: Kumao
authors.initials: K
authors.lastname: Uchida
authors.forename: Kouji
authors.initials: K
authors.lastname: Yukutake
authors.forename: Masashi
authors.initials: M
authors.lastname: Nakayama
authors.forename: Satoru
authors.initials: S
authors.lastname: Fujiie
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kuroda
authors.forename: Michio
authors.initials: M
authors.lastname: Kato
authors.forename: Harumasa
authors.initials: H
authors.lastname: Ohyanagi
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003510:Cyclohexanes; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D006207:Half-Life; D019344:Lactic Acid / Q000737:chemistry*; D008752:Methylene Chloride / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D010316:Particle Size; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*; D012717:Sesquiterpenes / Q000737:chemistry*; D013997:Time Factors; D014280:Triglycerides / Q000737:chemistry*
chemical_list: D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D012717:Sesquiterpenes; D014280:Triglycerides; D019344:Lactic Acid; C033616:poly(lactide); D008752:Methylene Chloride; D000077609:O-(Chloroacetylcarbamoyl)fumagillol