In order to improve the release pattern of chemotherapy drug and reduce the possibility of drug resistance,poly(ethylene glycol amine)(PEG)-modified alginate microparticles(ALG-PEG MPs)were developed then two differen...In order to improve the release pattern of chemotherapy drug and reduce the possibility of drug resistance,poly(ethylene glycol amine)(PEG)-modified alginate microparticles(ALG-PEG MPs)were developed then two different mechanisms were employed to load doxorubicin(Dox):1)forming Dox/ALGPEG complex by electrostatic attractions between unsaturated functional groups in Dox and ALG-PEG;2)forming Dox-ALG-PEG complex through EDC-reaction between the amino and carboxyl groups in Dox and ALG,respectively.Additionally,tuftsin(TFT),a natural immunomodulation peptide,was conjugated to MPs in order to enhance the efficiency of cellular uptake.It was found that the Dox-ALG-PEGTFT MPs exhibited a significantly slower release of Dox than Dox/ALG-PEG-TFT MPs in neutral medium,suggesting the role of covalent bonding in prolonging Dox retention.Besides,the release of Dox from these MPs was pH-sensitive,and the release rate was observably increased at pH 6.5 compared to the case at pH 7.4.Compared with Dox/ALG-PEG MPs and Dox-ALG-PEG MPs,their counterparts further conjugated with TFT more efficiently inhibited the growth of HeLa cells over a period of 48 h,implying the effectiveness of TFT in enhancing cellular uptake of MPs.Over a period of 48 h,Dox-ALG-PEG-TFT MPs inhibited the growth of HeLa cells less efficiently than Dox/ALG-PEG-TFT MPs but the difference was not significant(p>0.05).In consideration of the prolonged and sustained release of Dox,Dox-ALGPEG-TFT MPs possess the advantages for long-term treatment.展开更多
基金This study was funded by the National Natural Scientific Foundation of China(31670997)Natural Science Foundation of Hunan Province(2015JJ1007)Basic Research Program of Shenzhen City(JCYJ20160530193417959)。
文摘In order to improve the release pattern of chemotherapy drug and reduce the possibility of drug resistance,poly(ethylene glycol amine)(PEG)-modified alginate microparticles(ALG-PEG MPs)were developed then two different mechanisms were employed to load doxorubicin(Dox):1)forming Dox/ALGPEG complex by electrostatic attractions between unsaturated functional groups in Dox and ALG-PEG;2)forming Dox-ALG-PEG complex through EDC-reaction between the amino and carboxyl groups in Dox and ALG,respectively.Additionally,tuftsin(TFT),a natural immunomodulation peptide,was conjugated to MPs in order to enhance the efficiency of cellular uptake.It was found that the Dox-ALG-PEGTFT MPs exhibited a significantly slower release of Dox than Dox/ALG-PEG-TFT MPs in neutral medium,suggesting the role of covalent bonding in prolonging Dox retention.Besides,the release of Dox from these MPs was pH-sensitive,and the release rate was observably increased at pH 6.5 compared to the case at pH 7.4.Compared with Dox/ALG-PEG MPs and Dox-ALG-PEG MPs,their counterparts further conjugated with TFT more efficiently inhibited the growth of HeLa cells over a period of 48 h,implying the effectiveness of TFT in enhancing cellular uptake of MPs.Over a period of 48 h,Dox-ALG-PEG-TFT MPs inhibited the growth of HeLa cells less efficiently than Dox/ALG-PEG-TFT MPs but the difference was not significant(p>0.05).In consideration of the prolonged and sustained release of Dox,Dox-ALGPEG-TFT MPs possess the advantages for long-term treatment.
