PREPARATION OF PACLITAXEL STEALTH LIPOSOMES AND ITS TISSUE DISTRIBUTION IN MICE

AIM　To investigate the preparation of paclitaxel stealth liposomes and to observe its tissue distribution in mice. METHODS　The paclitaxel stealth liposomes were prepared by coprecipitation and microfluidization in two steps. The amphipathic polyethylene glycol-distearoyl phosphatidylethanolamine (PEG-DSPE) was added to modify the quality of liposomes membrane. The RP-HPLC was utilised for the determination of paclitaxel concentration in mice tissue. RESULTS　Stealth liposomes (S-liposomes) were ≤100 nm in mean diameter and encapsulated paclitaxel with ≥98% entrapping efficiency. Liposomal paclitaxel and free paclitaxel were injected intravenously at a dose of 5 mg paclitaxel.kg^-1 to mice. Prolonged circulation and reduced mononuclear phagocyte system uptake were achieved. After 24 h, up to 35% of the injected dose remains in the blood and less than 10% is taken up by the two major organs of the mononuclear phagocyte system, liver and spleen, compared with 10% and up to 50%, respectively, for conventional liposomes (C-liposomes) without amphipathic PEG-DSPE. The value of the area under the curve (AUC) of blood was approximately 2-fold higher than that of paclitaxel C-liposomes. CONCLUSION　Coprecipitation and microfluidization methods can highly increase the entrapping efficiency and decrease the size of the S-liposomes. The AUC of S-liposomes was increased and long circulation time can be reached after modification of lipid membrane with PEG-DSPE.