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.
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.
Chae
Gang Soo
GS
Department of Advanced Organic Materials Engineering, Chonbuk National University, 664-14, Duckjin Gu, Jeonju 561-756, Republic of Korea.
Lee
Jin Soo
JS
Kim
Seon Hwa
SH
Seo
Kwang Su
KS
Kim
Moon Suk
MS
Lee
Hai Bang
HB
Khang
Gilson
G
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
D018906:Antineoplastic Agents, Alkylating; D004655:Emulsions; D005079:Excipients; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002330:Carmustine