Preparation Of A New Antitumor Drug Etoposide-loaded Liposomes

Objective: To prepare etoposide-loaded liposomes, determine its drug loading and encapsulation efficiency, investigate its in vitro release compared with etoposide powder , and study its stability after sterilization.Method: The etoposide-loaded liposomes were prepared by film-ultrasonic wave dissolving techniques, the optimum formula was selected through uniform design. Scanning Electron Microscopy was used to observe its morphology and vesicle size. Dialytic method was used to determined its drug loading and encapsulation efficiency, vivo surroundings was imitated to do in vitro release experiment. Two sterilization methods were applied: moist heat and 60Co radiation, and 60Co radiation were selected two intensity, 4KGY and 6KGY. The etoposide-loaded liposomes were stored at 4癈 after sterilization, and vesicle size and percolation rate were used as parameters to test its stability.Results: Single factor investigation were used to determine that the quantity of etoposide was 5mg and phosphotipid was 50mg. Encapsulation efficiency being used as parameter, ultrasonic N the mass ratio ofphosphotipid to cholesterol and the volume of phosphate buffer being used as three factors, its optimum preparation of uniform design was: ultrasonic time 10 min, the mass ratio of phosphotipid to cholesterol 50mg:25mg, the volume of phosphate buffer 10 ml. The etoposide-loaded liposomes were regular in its morphology, and the maximum vesicle size were under 2 u m with the mean size of several hundreds nanometres. The drug loading of etoposide-loaded liposomes which prepared by its optimum formular was 574.3 H g/ml?0.7 JJ g/ml, the recovery was 98.99% + 1.97%, RSD was 0.044. The average encapsulation efficiency was 61.58% ?.83%. The in vitro release of etoposide-loaded liposomes added up to 96.13% ?1.11 % in 5Oh, and etoposide powder added up to 97.10% ?1.84% in 3h. After sterilization by moist heat and 60Co radiation, the liposomes being stored at 4癈, the vesicle size were not changed, but the percolation rate was high after moist heat sterilization. Through 60Co 4KGY radiation sterilization the average percolation rate was 3.43% after being stored 30 days and 6.75% after being stored 60 days, through 60Co 6KGY radiation sterilization the average percolation rate was 5.37% after being stored 30 days and 9.46% after being stored 60 days.Conclusion: The etoposide-loaded liposomes prepared by film-ultrasonic wave dissolving techniques were regular in its morphology, and their vesicle size weresmall and equal. Through in vitro release experiments, the etoposide-loaded liposomes were conformed to be long-acting and sustained -release preparation. The stability was poor after moist heat sterilization and good after 60Co radiation sterilization. In the future, in order to increase encapsulation efficiency, the new methods and techniques would be selected and the new excipients would be used. Through the experiments done and will be done, the etoposide-loaded liposomes should have a good future in clinical use.