Preparation And Pharmacokinetics Of BD/PTX-loaded-circulating Targeting Liposomes

The purpose of this article is to prepare and characterization of long-circulating targeting liposomes containing α-hederin(BD)and paclitaxel(PTX)with an optimal ratio,in order to target tumor tissues and achieve the purpose of reducing toxicity and increasing efficiency.The new nanoliposomes constructed show certain significance for reversing tumor multidrug resistance(MDR).In this paper,the best ratio of the two drugs is determined through cell experiments.Using the film dispersion method,the formulation for long-circulating targeting liposomes(GAL-SSL-BD-PTX)and conventional liposomes(SSL-BD-PTX)was screened by the factors,the organic solution,types of phospholipids,hydration solvent,hydration temperature,hydration time,drug to phospholipid ratio,different phospholipid ratio,ultrasonic power and ultrasonic time.To establish a simple and efficient method for the determination of α-hederin and paclitaxel in liposomes using high performance liquid chromatography(HPLC),ultraviolet spectrophotometer(UV-Vis),particle size analyzer,transmission electron microscopy(TEM),and atomic force microscopy(AFM).The average particle size of GAL-SSL-BD-PTX was(125.9±0.35)nm,the encapsulation efficiency for BD and PTX was(99.81±0.84)%,and(98.93±1.16)%,respectively.The morphology of liposomes was spherical,with a particle size of about 130 nm.The particles were stable for 30 d when kept at 4 ℃ in the dark.To establish a rapid and sensitive liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for the determination of α-hederin and paclitaxel in rat plasma.Glycyrrhizic acid and docetaxel were used as internal standards,and the protein was removed by methanol precipitation.The samples were detected by Agilent 1290 series 6460 triple quadrupole LC/MS mass spectrometer multiplemonitoring(MRM)scanning method.Rats were injected through tail vein with equal doses(PTX10mg·kg-1,BD5mg·kg-1)of SSL-BD-PTX,GAL-SSL-BD-PTX,α-hederin and paclitaxel solution.The pharmacokinetic parameters of each group were calculated through DAS ver 3.0 software.Compared with the solution group,the average residence time of PTX in Group C and Group D was increased by 3.03 and2.98 times,and the average residence time of BD was increased by 1.9 and 2.7 times,respectively,showing a significant long-circulating effect.The Cmax of BD in groups C and D was 2.6 and 3.0 times than that of the solution group,and the Cmax of PTX was 3.3 times and 1.1 times than that of the solution group,respectively.We concluded that the liposomes can significantly increase the blood concentration and circulating time of the drugs.