Studies On Freeze-dried Liposome Of Lomustine

The HPLC analytical method for CCNU in vitro was developed. The solubilities of CCNU in water and PBS with different pH and the apparent partition coefficient in n-octyl alcohol/water was determined by HPLC. The HPLC method for the content of CCNU in liposomes was established. The entrapment efficiency of CCNU liposome was determined by microcolumn centrifuge-HPLC method.The CCNU liposome was prepared by ethanol injection method. The single factor investigation and the orthogonal design were adopted to obtain the optimized prescription, the entrapment efficiency of CCNU liposome was above 80%.To resolve the instability problem of liposome dispersion, freeze-drying (lyophilization) technique was utilized to prepare freeze-dried proliposome. The technology of freeze-dried especially on the kinds and ratio of cryoprotectants had been researched.The physicochemical properties of freeze-dried CCNU liposome were studied. The liposome was spheroidal and uniform, the volume diameters of CCNU liposome suspension and freeze-dried product were (155±21) nm and (185±30) nm respectively; the pH value was not changed notably, closed to 7.4; the entrapment efficiency of these were (82.06±1.1)% and(78.39±1.8)% differently; the drug loading capacity of these were (2.22±1.4)% and (0.52±6.9)%The results of stability tests indicated that the CCNU freeze-dried liposome was sensitive to high temperature and strong light. There was not significant change in the accelerated test and the long test.The security investigation indicated that the CCNU liposome injection was non-irritant and non-hematolytic, the preparation met the regulations of the i.v. administration.The HPLC method of CCNU liposome in blood plasma and tissues was established. After i.v. administrated CCNU suspension and liposomes to mice, respectively, the drug concentrations in different tissues were monitored by HPLC. The pharmacokinetic processes in mice for the two preparations were both accorded with two compartmental models. Compared with CCNU suspension, the liposome had longer half-life and higher bioavailability. The levels of CCNU liposome in liver, spleen, lung and brain were higher than that of suspension group.