Biodistribution of liposomes of terbutaline sulfate in guinea pigs

A series of liposomes was prepared with various lipid (egg phosphatidyl cho line [egg PC], phosphatidyl glycerol [PG], dipalmitoyl phosphatidyl choline [DPPC], distearoyl phosphatidyl choline [DSPC], dipalmitoyl phosphatidyl g lycerol [DPPG], phosphatidyl ethanolamine [PE], cholesterol [CH], and stear ylamine [SA]) compositions, such as egg PC:PG:CH (55:5:40), DPPC:PG:CH (55: 5:40), DSPC:DSPG:CH (55:5:40) egg PC:SA:CH (55:5:40), DSPE:DSPG:CH (55:5:40 ) in molar ratio. Liposomal formulations were administered to guinea pigs i ntravenously; 3 hr after the treatment, serum samples and various organs (e .g., liver, spleen, lung) were removed and analyzed for drug concentration by a high-performance liquid chromatographic (HPLC) method. Based on the ab ove study, a liposomal preparation with better lung specificity was selecte d, and the time profile of these liposomes was determined in guinea pigs. T hree hours postadministration, a significant difference in blood levels was observed between free terbutaline sulfate and the various liposomal formul ations. Localization of the drug in the lungs increased considerably when e ncapsulated drug was used, and the highest percentage localization was obse rved with DSPC:DSPG:CH (55:5:40) liposomes. The percentage recovery of the drug in the lungs with egg PC:CH:SA (55:40:5) liposomes did not change sign ificantly when compared with egg PC:CH:PG (55:40:5) liposomes. To establish the time course of disposition of the liposomes, DSPC:DSPG:CH (55:5:40) li posomes were selected. Terminal half-life t(1/2) of the drug in blood with free drug solution was about 12 hr, whereas with liposomes, a twofold incre ase in t(1/2) was observed. The disposition data indicated that the clearan ce of the drug was delayed by 1.5 times when incorporated into liposomes.