Preparation and evaluation of folate-decorated pH-responsive doxorubicin liposomes

YE Peng; RONG Pei-pei; CHEN Li; SHI Cai

Abstract：Objective:To prepare and characterize folate-decorated pH-responsive doxorubicin liposomes (FRLD) and evaluate their quality.Methods:FRLD were prepared by the ammonium sulfate gradient method.Taking entrapment efficiency as an index,the technical conditions were optimized by orthogonal test.Unloaded doxorubicin was separated from the liposomes by sepharose CL-4B chromatography and HPLC method was used to determine the entrapment efficiency of FRLD.The shape,particle size and zeta-potential of FRLD were investigated by transmission electron microscope and laser scatter.The drug release from liposomes in PBS (pH 7.4 and pH 5.5) was monitored by dialysis method.The change of particle size of FRLD over time was monitored in PBS of different pH values at 37 ℃.Results:The obtained FRLD were round and large unilamellar vesicles with average size of (153.8 ± 2.62) nm,zeta potential of-(24.62 ± 2.28) mV and entrapment efficiency of 89.45％.The results of drug release test showed that FRLD exhibited minimal DOX leakage in pH 7.4 PBS after 24 h incubation,and more than 90％ of the encapsulated DOX still retained in the liposomes.While in pH 5.5 PBS,FRLD released more than 90％ DOX after 24 h incubation and showed stronger pH response.And furthermore,the mean diameter of FRLD was significantly increased at low pH (5.5) at 37 ℃,which indicated vesicle aggregation and membrane fusion.Conclusion:FRLD prepared by the ammonium sulfate gradient method can achieve high entrapment efficiency and remarkable pH response.