Establishment And Evaluation Of RHDL-Paclitaxel Complexes

Purpose:Prepare reconstituted high-density lipoprotein particles carrying paclitaxel(rHDL-PTX).The physical and chemical characteristics were investigated and evaluated comprehensively to prove the advantage of drug loaded nanoparticles,and the anti-tumor effects were studied in tumor cells in vitro.Methods:rHDL-PTX was prepared by cosonication.Electron microscopy and dynamic light scattering(DLS)were used to determine themorphology and the size of the aqueous dispersion of nanoparticles.The enveloping efficiency and drug loading capacity were determined by ultraviolet specterphotometry.The release pattern of the drug-loaded nanoparticles in vitro is measured with the high performance liquid chromatography(HPLC).Cellular localization and fluoresence intensity of rHDL was monitored by confocal microscopy.Antitumor effect and the cellular uptake of free paclitaxel,rHDL-PTX and rHDL were studied on the cell lines secreting SR-BI+/-,respectively.Results:The stability of rHDL-PTXs prepared from different ratio of DMPC and Apo A-I were studied to determine the most suitable ratio.rHDL-PTXs by the ratio of 20:1 were stable till 14 days.rHDL-PTXs had a spherical shape and they were under 50 nm size.The drug-loading efficiency was 96.1307±3.4180%,and the drug loading eapacity was 14.6810±0.9018%.It has significant effect of controlled-release formulation.rHDLs were taken up by tumor cells with SR-BI+.Free rHDLs is nontoxic vesicles.The rHDL-PTX had antitumor effect,and its advantage was obviously consistent with the level of the expression of SR-BI.It had better antitumor effect on the cell lines with SR-BI+ than SR-BI-.Conclusions:1.This project showed that the rHDL-PTX had a nearly smoothly spherical shape,the ideal diameter,the stable shape,and a slow-release,targeting features.2.The cell experiments in vitro showed that the rHDL-PTX had antitumor effect,and its advantage was obviously consistent with the level of the expression of SR-BI.It had better antitumor effect on the cell lines with SR-BI+ than SR-BI-.