| A novel p H-and responsive stearic acid grafted-Bletilla striata polysaccharide amphiphilic copolymer(BSP-ss-SA)was synthesized and loaded docetaxel and then DTX loaded micelle was prepared.The feasibility of BSP-ss-SA as an antitumor drug carrier was studied.Firstly,BSP-COOH was synthesized with succinic anhydride with high reactive activity.Then BSP-COOH and cystamine containing disulfide bond reacted to BSP-CYS by amidation.Finally,BSP-ss-SA was prepared by amidation between BSP-CYS and stearic acid(SA).The structure of BSP,BSP-COOH,BSP-CYS and BSP-ss-SA were characterized by infrared spectroscopy(FT-IR)and nuclear magnetic resonance(~1H-NMR).The degree of substitution of succinic anhydride grafted onto BSP was calculated by acid-base titration.The degree of substitution of cystamine(CYS)grafted onto BSP-COOH and stearic acid(SA)grafted onto BSP-CYS was both calculated by~1H-NMR.The BSP-ss-SA micelle were prepared by dialysis method.The size,zeta potential and isoelectric point of BSP-ss-SA were measured by by Malvern particle size analyzer.The CAC of BSP-ss-SA was determined by fluorescence spectrometry.The results showed that BSP-ss-SA could self-assemble into micelles in water and the particle size increased significantly under reducing conditions(10 mM dithiothreitol(DTT))and acidic environment(pH 5.0 PBS).The isoelectric point and CAC of BSP-ss-SA micelle were 3.0 and 76.36?g/mL,respectively.Docetaxel was used as model drug and DTX loaded micelle was prepared by emulsion solvent evaporation method.The results showed that drug loading content(LC)and encapsulation efficiency(EE)of DTX loaded micelle were 5.94%and 72.75%,respectively.Glycine could increase the drug loading content and encapsulation efficiency.The in vitro release of DTX loaded micelle was measured by dialysis bag method.The results showed that DTX release from of DTX loaded micelle was affected by pH and amount of reducing agent in released medium.The accumulative release amount of DTX showed higher in the reduction and pH 5.0 release medium.MTT showed that the blank BSP-ss-SA micelles(40?g/m L)did not inhibit significantly growth of HepG2 cells and the cell viability was more than 85%.Compared with DTX solution,the inhibitory effect of DTX loaded micelle on HepG2cells was more obvious.In vivo experiment demonstrated the antitumor effect of the DTX loaded micelle was stronger than that in DTX solution in 5 days.This is probably due to that the small size and large specific surface area of DTX-loaded micelle increased residence time in vivo.In addition,it may be that BSP-ss-SA has the pH and reduction responsive characteristic which could triggered BSP-ss-SA to crack rapidly in tumor cells and increased DTX concentration at target site to improve the antitumor effect.In conclusion,the preparation method of BSP-ss-SA is feasible.BSP-ss-SA can self-assemble to form nanoparticles in water and load antitumor drug responding to pH and reduction agent.BSP-ss-SA has higher safety.Hence,BSP-ss-SA can be used as a new carrier of hydrophobic drug to achieve drug targeting release. |
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