合成制备了不同分子量的PLA-PEG-PLA嵌段共聚物,并应用1 H NMR对其进行测试表征.然后将共聚物作为亲水性添加剂,用自行研发的中空纤维膜纺丝机对应制备了不同的PLA共混中空纤维膜.对制成的中空纤维膜进行水通量、残留率、水接触角、抗...合成制备了不同分子量的PLA-PEG-PLA嵌段共聚物,并应用1 H NMR对其进行测试表征.然后将共聚物作为亲水性添加剂,用自行研发的中空纤维膜纺丝机对应制备了不同的PLA共混中空纤维膜.对制成的中空纤维膜进行水通量、残留率、水接触角、抗污染性能等测试以及SEM观察,研究了该添加剂对PLA中空纤维膜各种性能的影响.结果发现,制成的中空纤维膜超滤性能优异,添加PLA-PEG-PLA嵌段共聚物会提高PLA中空纤维膜的抗污染性能,并且共聚物分子量越大,中空纤维膜的亲水性越好,抗污染性能越好.展开更多
Drug delivery by nanocarriers requires characterizations of suitable particle size, high drug loading and safety. In this work, we prepared an amphiphilic dendrimer modified PEG-PLA mixed nanoparticles（NPs） by a dou...Drug delivery by nanocarriers requires characterizations of suitable particle size, high drug loading and safety. In this work, we prepared an amphiphilic dendrimer modified PEG-PLA mixed nanoparticles（NPs） by a double emulsion-solvent evaporation（DESE） method. The particle size and drug encapsulation efficacy（EE） were compared to evaluate and optimize the preparation parameters. The mixed NPs had average size ranging from（102±1） nm to（137±5） nm, and the zeta potential turned to positive with incorporation of the amphiphilic dendrimer. The NPs showed different EE of docetaxel（DTX） and paclitaxel（PTX） with higher affinity to more lipophilic PTX. The blank mixed NPs showed little cytotoxicity, and the DTX-loaded NPs could effectively facilitate the antiproliferation activity on PC-3 cells. The NPs could be used as an effective drug delivery system, and its anti-tumor effect is worthy of further study.展开更多
The presence of protein corona on the surface of nanoparticles modulates their physiological interactions such as cellular association and targeting property.It has been shown that α-mangostin(αM)-loaded poly(ethyle...The presence of protein corona on the surface of nanoparticles modulates their physiological interactions such as cellular association and targeting property.It has been shown that α-mangostin(αM)-loaded poly(ethylene glycol)-poly(l-lactide)(PEG-PLA)nanoparticles(NP-αM)specifically increased low density lipoprotein receptor(LDLR)expression in microglia and improved clearance of amyloid beta(Aβ)after multiple administration.However,how do the nanoparticles cross the blood‒brain barrier and access microglia remain unknown.Here,we studied the brain delivery property of PEG-PLA nanoparticles under different conditions,finding that the nanoparticles exhibited higher brain transport efficiency and microglia uptake efficiency afterαM loading and multiple administration.To reveal the mechanism,we performed proteomic analysis to characterize the composition of protein corona formed under various conditions,finding that both drug loading and multiple dosing affect the composition of protein corona and subsequently influence the cellular uptake of nanoparticles in b.End3 and BV-2 cells.Complement proteins,immunoglobulins,RAB5A and CD36 were found to be enriched in the corona and associated with the process of nanoparticles uptake.Collectively,we bring a mechanistic understanding about the modulator role of protein corona on targeted drug delivery,and provide theoretical basis for engineering brain or microglia-specific targeted delivery system.展开更多
通过酯键将末端羧基化的聚乙二醇-聚乳酸(PEG-PLA)与紫杉醇连接,合成了前体化合物PEG-PLA-PTX(1),总收率约56%。芘荧光探针法测得1水溶液的临界胶束浓度为3.98×10-4 g/L,1在p H 7.4磷酸盐缓冲液中能缓慢释放出紫杉醇。体外抗肿瘤...通过酯键将末端羧基化的聚乙二醇-聚乳酸(PEG-PLA)与紫杉醇连接,合成了前体化合物PEG-PLA-PTX(1),总收率约56%。芘荧光探针法测得1水溶液的临界胶束浓度为3.98×10-4 g/L,1在p H 7.4磷酸盐缓冲液中能缓慢释放出紫杉醇。体外抗肿瘤试验表明,1具有抑制鼻咽癌LMP1细胞增殖的作用。展开更多
文摘合成制备了不同分子量的PLA-PEG-PLA嵌段共聚物,并应用1 H NMR对其进行测试表征.然后将共聚物作为亲水性添加剂,用自行研发的中空纤维膜纺丝机对应制备了不同的PLA共混中空纤维膜.对制成的中空纤维膜进行水通量、残留率、水接触角、抗污染性能等测试以及SEM观察,研究了该添加剂对PLA中空纤维膜各种性能的影响.结果发现,制成的中空纤维膜超滤性能优异,添加PLA-PEG-PLA嵌段共聚物会提高PLA中空纤维膜的抗污染性能,并且共聚物分子量越大,中空纤维膜的亲水性越好,抗污染性能越好.
基金National Natural Science Foundation of China(Grant No.81473156,81673365,81273454)Doctoral Foundation of the Ministry of Education(Grant No.20130001110055)National Key Basic Research Program(Grant No.2013CB932501)
文摘Drug delivery by nanocarriers requires characterizations of suitable particle size, high drug loading and safety. In this work, we prepared an amphiphilic dendrimer modified PEG-PLA mixed nanoparticles（NPs） by a double emulsion-solvent evaporation（DESE） method. The particle size and drug encapsulation efficacy（EE） were compared to evaluate and optimize the preparation parameters. The mixed NPs had average size ranging from（102±1） nm to（137±5） nm, and the zeta potential turned to positive with incorporation of the amphiphilic dendrimer. The NPs showed different EE of docetaxel（DTX） and paclitaxel（PTX） with higher affinity to more lipophilic PTX. The blank mixed NPs showed little cytotoxicity, and the DTX-loaded NPs could effectively facilitate the antiproliferation activity on PC-3 cells. The NPs could be used as an effective drug delivery system, and its anti-tumor effect is worthy of further study.
基金This work was supported by National Natural Science Foundation of China(No.81722043,92068111,81973272,81803089,81903582,82073836)National Science and Technology Major Project(2018ZX09734005,2017ZX09304016,China)grant from Shanghai Science and Technology Committee(19410710100,18YF1413400,China).
文摘The presence of protein corona on the surface of nanoparticles modulates their physiological interactions such as cellular association and targeting property.It has been shown that α-mangostin(αM)-loaded poly(ethylene glycol)-poly(l-lactide)(PEG-PLA)nanoparticles(NP-αM)specifically increased low density lipoprotein receptor(LDLR)expression in microglia and improved clearance of amyloid beta(Aβ)after multiple administration.However,how do the nanoparticles cross the blood‒brain barrier and access microglia remain unknown.Here,we studied the brain delivery property of PEG-PLA nanoparticles under different conditions,finding that the nanoparticles exhibited higher brain transport efficiency and microglia uptake efficiency afterαM loading and multiple administration.To reveal the mechanism,we performed proteomic analysis to characterize the composition of protein corona formed under various conditions,finding that both drug loading and multiple dosing affect the composition of protein corona and subsequently influence the cellular uptake of nanoparticles in b.End3 and BV-2 cells.Complement proteins,immunoglobulins,RAB5A and CD36 were found to be enriched in the corona and associated with the process of nanoparticles uptake.Collectively,we bring a mechanistic understanding about the modulator role of protein corona on targeted drug delivery,and provide theoretical basis for engineering brain or microglia-specific targeted delivery system.
文摘通过酯键将末端羧基化的聚乙二醇-聚乳酸(PEG-PLA)与紫杉醇连接,合成了前体化合物PEG-PLA-PTX(1),总收率约56%。芘荧光探针法测得1水溶液的临界胶束浓度为3.98×10-4 g/L,1在p H 7.4磷酸盐缓冲液中能缓慢释放出紫杉醇。体外抗肿瘤试验表明,1具有抑制鼻咽癌LMP1细胞增殖的作用。
