The Study Of Encapsulation Of Azidothymidine In Liposomes Containing Galactosylceramide And Its Pharmacokinetics

To investigate the practicability of galactosylceramide (GalCer) serving as new targeting delivery carrier for antiHIV, azidothymidine (AZT) was encapsulated in liposomes containing GalCer (AZT-GalCer) and the pharmacokinetics and tissue distribution of AZT-GalCer and free AZT were observed in mice.AZT-GalCer was prepared by double emulsion and its encapsulation ratio were up to 72.5%. The results of electron micrography showed that the AZT-GalCer liposomes was consisted of spherical or similar to spherical small unilamellar vesicles, the size was 60~270nm and its D50 was 140nm.A rapid, accurate and stable RP-HPLC method was established for the determination of AZT in plasma and tissue. The calibration curves of AZT were linear separately within the concentration range of 0.02~20mg/L. The relative standard deviations for within-day and between-days were all less than 10%. The relative recovery of the method were from 88.9% to 102.3%. The limit of quantitation of the assay is 5 ng/ml in plasma and 10 ng/g in tissue.The pharmacokinetics and tissue distribution was observed following the administration of a single intravenous dose (10 mg-kg-1) of AZT-GalCer or AZT in mice. Much higher concentration of AZT in mice injected AZT-GalCer were found in plasma after 30min and it was ten times as high as in mice injected with AZT. On the other hand, Ke decreased significantly from 0.037 to 0.021, ti/2Ke increased significantly from 19min to 35min, and AUC was 2.77 times as high as in mice injected with AZT. The changes of tissue distribution were observed. The concentration in thymus in mice treated with AZT- GalCer was 3.2, 7 and 14 times as high as in mice treated with AZTat 5min, 90min and at 120min respectively. The concentration in spleen was only 0.29 0.13 g-g-1 at 90min and was not detected at 120min in mice injected with AZT, while it was 1.24 + 0.24 g-g-1, 0.47 + 0.08 g-g-1 and 0.32 + 0.06 u g-g'1 at 120, 150, 1 SOmin in AZT-GalCer mice respectively. The concentration in liver was only 0.28 ?0.04 g-g-1 at 60min and was not detected at 90min in AZT mice, while it was 0.76 + 0.29 g-g-1 and 0.32 + 0.15 g-g-1 at 60min and 90min in AZT- GalCer mice respectively.AZT-GalCer serving as a dilivery carrier cound prolong the effective concentration of AZT in plasma, greatly enhance the drug accumulation in targeted immune organ in vivo. AZT- GalCer might have great therapeutic potential for antiHIV.