Ethinylestradiol liposome preparation and its effects on ovariectomized rats' osteoporosis

Abstract

Ethinylestradiol liposome (EEL) was prepared by thin film evaporationextrusion technique and its effects on ovariectomized rat osteoporosis were investigated. The liposomes were characterized with clear homogeneous lamellar vesicles and had the average size of 200±1.5nm. The long term stability of liposome formulations were tested over a 28-day period at 4°C and ethinylestradiol retention was approximately 80% up to 28 day. Release data of ethinylestradiol was tested in PBS pH 7.4 at 37°C using a dialysis method and its release profiles were biphasic, showing a relatively large burst effect over the first four hours, followed by a slower release phase. Ovariectomized rat model was used to investigate EEL effects on osteoporosis. After three months post-surgery, the rats were divided into two groups and injected intraperitoneally (IP) with 2 μg per kilogram per day of either free ethinylestradiol (EE) or encapsulated ethinlyestradiol (EEL). At termination of one month IP injection, the rats were killed and the bone mineral density (BMD) and alkaline phosphatase (ALP) were measured. BMD value in free EE group increased by 20.3 %, while it increased by 37.8 % in EEL group. According to ALP value, the two treatment groups increased by 28.6 % and 42.0 %, respectively. These data indicated that ethinlyetradiol liposome had better effect than that of free ethinylestradiol did in treatment of the ovariectomized rats' osteoporosis. But the metabolites and biodistribution of ethinylestradiol liposome in vivo need to investigate in the further research work. © 2011 Informa Healthcare USA, Inc.