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.