title: Enhancement of the stability of BCNU using self-emulsifying drug delivery systems (SEDDS) and in vitro antitumor activity of self-emulsified BCNU-loaded PLGA wafer.
abstract: The main purpose of this study was to develop self-emulsifying drug delivery systems (SEDDS) for the improvement of the stability of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) after released from poly (D,L-lactide-co-glycolide) (PLGA) wafer and to evaluate its in vitro antitumor activity against 9L gliosarcoma cells. The in vitro stability test of BCNU was characterized by the BCNU amount in phosphate buffered saline (PBS, pH 7.4) at 37 degrees C. SEDDS increased in vitro half-life of BCNU up to 130 min compared to 45 min of intact BCNU. Self-emulsified (SE) BCNU was fabricated into wafers with flat and smooth surface by compression molding. In vitro release of BCNU from SE BCNU-loaded PLGA wafer was prolonged up to 7 days followed first order release kinetics. Beside, the cytotoxicity of SE BCNU-loaded PLGA wafer against 9L gliosarcoma cells was higher than intact BCNU-loaded PLGA wafer which is more susceptible to hydrolysis. SE BCNU degraded much more slowly than the intact BCNU in PLGA matrix at 25 degrees C. These results strongly suggest that the self-emulsion system increased the stability of BCNU after released from PLGA wafer. From these results, it could be expected that the penetration depth of BCNU could be improved in brain tissue using self-emulsion system.
authors: Department of Advanced Organic Materials Engineering, Chonbuk National University, 664-14, Duckjin Gu, Jeonju 561-756, Republic of Korea.
authors: Gang Soo
authors: GS
authors: Chae
authors: Jin Soo
authors: JS
authors: Lee
authors: Seon Hwa
authors: SH
authors: Kim
authors: Kwang Su
authors: KS
authors: Seo
authors: Moon Suk
authors: MS
authors: Kim
authors: Hai Bang
authors: HB
authors: Lee
authors: Gilson
authors: G
authors: Khang
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000032:analysis* / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology; D002330:Carmustine / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D004355:Drug Stability; D004356:Drug Storage; D004655:Emulsions; D005079:Excipients; D018316:Gliosarcoma / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D019344:Lactic Acid; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004655:Emulsions; D005079:Excipients; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002330:Carmustine