Preparation of freeze-dried chitosan-liposome containing L-dopa and pharmacokinetics in rats after oral administration

Aim ：To prepare chitosan-coated L-dopa liposomes，and to optimize the formulation and freeze-drying processing parameters of L-dopa liposomes. Methods ：The liposomes were prepared by using reverse phase evaporation followed by freeze-drying，and effects of the factors on the entrapment efficiency of L-dopa liposome were studied.Pharmacokinetics of L-dopa in rats receiving oral dosing of L-dopa solution and chitosan-coated liposomes were investigated after HPLC determination of L-dopa levels in rats plasma. Results ：The optimized freeze-drying formulation composed of 50 mg/mL of phosphatidyl choline (PC)，0.17% chitosan，2% sucrose as freeze-drying protectant，and a ratio of 1∶10 of drug loading to lipid.Entrapment efficiency(EE) was calculated to be (34.34±0.65)%(n=6).Compared with L-dopa solution，c _max was delayed and higher levels maintained for a longer period after oral administration of L-dopa liposomes in rats.Moreover，the magnitude of the increased L-dopa dioavailability in rats was more than 400% of that of L-dopa solution. Conclusion ：Freeze-dried liposomal preparation with EE of more than 30% was obtained by the proposed approch.Chitosan coated L-dopa liposomes increased the L-dopa bioavailability in rats.