The different fate of liposomes among species has been discovered and mentioned in many studies, but the underlying mechanisms have not been explored. In the present work, we concentrated on the in vivo fate of PEGyla...The different fate of liposomes among species has been discovered and mentioned in many studies, but the underlying mechanisms have not been explored. In the present work, we concentrated on the in vivo fate of PEGylated liposomes (sLip) in three commonly used species (mice, rats, and dogs). It was exhibited that the accelerated blood clearance (ABC) phenomenon and hypersensitivity in large animals (beagle dogs) were much more significant than that in rodents. We demonstrated that anti-PEG IgM (partially) and complement (mostly) determined the elimination of sLip and linked the distinct interspecies performances with the diverse complement capacity among species. Based on the data from animals and clinical patients, it was revealed that the fate of sLip in large animals was closer to that in humans, for the sufficient complement capacity could expose the potential adverse reactions caused by anti-PEG antibodies. Our results suggested that the distinctive interspecies performances of sLip were highly related to the physiological variabilities among species, which should not be overlooked in the innovation and translation of nanomedicines.展开更多
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
The accelerated blood clearance(ABC) phenomenon which is induced by repeated injection of poly(ethylene glycol)(PEG)-coated colloidal carriers gives clinical challenge to the promising drug delivery system. It is nece...The accelerated blood clearance(ABC) phenomenon which is induced by repeated injection of poly(ethylene glycol)(PEG)-coated colloidal carriers gives clinical challenge to the promising drug delivery system. It is necessary to decrease this unexpected immunological response.A novel 4-arm poly(ethylene glycol-5000)4-cholesteryl methyl amide(4-arm PEG5000-CHMA)has been synthesized. The structure of 4-arm PEG5000-CHMA was confirmed by IR and 1H-NMR spectrum. The pharmacokinetics of the tocopheryl nicotinate(TN)-loaded nanoemulsions modified with 4-arm PEG5000-CHMA or/and 1, 2-distearoyl-Sn-glycero-3-phosphoethanolamine-n-[methoxy(poly-ethyleneglycol)-2000](mPEG2000-DSPE) have been studied. Furthermore, the ABC phenomenon has been detailed investigated in rats by TN-loaded nanoemulsions modified with 4-arm PEG5000-CHMA and mPEG2000-DSPE(CPNE). The plasma levels of TN and anti-PEG IgM antibody were determined by HPLC and ELISA, respectively.The circulation time of the CPNEs were comparable to the mPEG2000-DSPE coated nanoemulsions. Moreover, the ABC phenomenon can be decreased by CPNEs. This study designs a method to decrease the ABC phenomenon and develops a clinical promising nanoemulsion for therapeutic or imaging purpose.展开更多
基金National Natural Science Fund of China(32330058,82125035)Shanghai Education Commission Major Project(2021-01-07-00-07-E00081,China).
文摘The different fate of liposomes among species has been discovered and mentioned in many studies, but the underlying mechanisms have not been explored. In the present work, we concentrated on the in vivo fate of PEGylated liposomes (sLip) in three commonly used species (mice, rats, and dogs). It was exhibited that the accelerated blood clearance (ABC) phenomenon and hypersensitivity in large animals (beagle dogs) were much more significant than that in rodents. We demonstrated that anti-PEG IgM (partially) and complement (mostly) determined the elimination of sLip and linked the distinct interspecies performances with the diverse complement capacity among species. Based on the data from animals and clinical patients, it was revealed that the fate of sLip in large animals was closer to that in humans, for the sufficient complement capacity could expose the potential adverse reactions caused by anti-PEG antibodies. Our results suggested that the distinctive interspecies performances of sLip were highly related to the physiological variabilities among species, which should not be overlooked in the innovation and translation of nanomedicines.
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supported by the National Natural Science Foundation of China (Grant No. 81072602, Grant No. 81373334)
文摘The accelerated blood clearance(ABC) phenomenon which is induced by repeated injection of poly(ethylene glycol)(PEG)-coated colloidal carriers gives clinical challenge to the promising drug delivery system. It is necessary to decrease this unexpected immunological response.A novel 4-arm poly(ethylene glycol-5000)4-cholesteryl methyl amide(4-arm PEG5000-CHMA)has been synthesized. The structure of 4-arm PEG5000-CHMA was confirmed by IR and 1H-NMR spectrum. The pharmacokinetics of the tocopheryl nicotinate(TN)-loaded nanoemulsions modified with 4-arm PEG5000-CHMA or/and 1, 2-distearoyl-Sn-glycero-3-phosphoethanolamine-n-[methoxy(poly-ethyleneglycol)-2000](mPEG2000-DSPE) have been studied. Furthermore, the ABC phenomenon has been detailed investigated in rats by TN-loaded nanoemulsions modified with 4-arm PEG5000-CHMA and mPEG2000-DSPE(CPNE). The plasma levels of TN and anti-PEG IgM antibody were determined by HPLC and ELISA, respectively.The circulation time of the CPNEs were comparable to the mPEG2000-DSPE coated nanoemulsions. Moreover, the ABC phenomenon can be decreased by CPNEs. This study designs a method to decrease the ABC phenomenon and develops a clinical promising nanoemulsion for therapeutic or imaging purpose.
