Investigation On Synthesis Of Bletilla Striata Polysaccharide Derivatives And Anticancer Drug Of Docetaxel-loaded Delivery System

The aim of the present study was to improve B.striata polysaccharides hydrophobic property,Stearic acid(SA)were used to modify water-soluble B.striata polysaccharides,Stearic acid(SA)-modified B.striata polysaccharides amphiphilic copolymers(SA-BSPs)were prepared.Fourier Transform Infrared Spectroscopy(FTIR)and 1H Nuclear Magnetic Resonance Spectroscopy(lH NMR)were used to describe SA-BSPs group,the substitued degree of the SA-BSPs group was determined by the peak area of lH NMR.Docetaxel as model drug,Docetaxel-loaded SA-conjugated BSPs(DTX-SA-BSPs)copolymer micelles were formulated by solvent evaporation and characterized in terms of particle diameter,particle size distribution and zeta potential.Drug loading capacity(LC)and encapsulation efficiency(EE)were determined by using high performance liquid chromatography(HPLC).The in vitro release of DTX from DTX-SA-BSPs copolymer micelles was investigated by using the dialysis method.Pharmacokinetics and tissue distribution studies of DTX-SA-BSPs copolymer micelles and docetaxel injection,after intravenous administration to conscious male ICR mices were studied.The DTX concentration in vivo were detected by using HPLC and the area of concentration–time curve was also calculated.Pharmacokinetics parameters were calculated by DAS 2.1 software.The biosafety of SA-BSPs copolymers was evaluated by MTT assay and hemolysis Assay.The FTIR and 1H NMR results indicated that SA was successfully conjugated with BSPs and the substitued degree of the SA-BSPs group was 12.94 %.DTX-SA-BSPs copolymer micelles had an average size of(97.01 ± 3.17)nm with zeta potential in the range of-(19.56 ± 0.22)mV.The drug encapsulation and loading capacity was(81.11 ± 0.18)% and(9.13 ± 0.17)% respectively.The results showed that DTX was gradually released from the DTX-SA-BSPs copolymer micelles in pH 7.4 phosphate buffer saline.The release percentage of DTX from DTX-SA-BSPs copolymer micelles was(66.93 ± 1.79)% in 48 h,respectively.The DTX-SA-BSPs copolymer micelles exhibited a sustained release of DTX.The average cell line inhabition of DTX-SA-BSPs polymer micelles were(83.7 ± 1.0)% at 0.5μg/mL after 72 h incubation.The pharmacokinetics of ICR mices in vivo results showed that the DTX-SA-BSPs copolymer micelles also maintained a higher drug concentration and a constant release rate for a relatively longer time than docetaxel injection(MRT 1.42 ± 0.02 h vs 1.82 ± 0.11 h,p<0.05).The absolute bioavailability of DTX-SA-BSPs copolymer micelles was shown to be 1.39-fold higher than that of docetaxel injection(AUC0-∞ 65.39 ± 5.21 μg/mL·h vs 47.73 ± 0.49 μg/mL·h,p<0.05).In tested organs,the DTX contents of DTX-SA-BSPs copolymer micelles were higher than that of docetaxel injection in heart,liver,and lung.But,it was lower than that of docetaxel injection in kidey and spleen.These results indicated that DTX-SA-BSPs copolymer micelles could alter the tissue distribution,this might be an encouraging stragety to cure lung cancer.