[Objectives]To prepare 20(S)-protopanaxadiol PLGA nanoparticles(20(S)-PPD-PLGA-NPs).[Methods]20(S)-PPD-PLGA-NPs were prepared by emulsion solvent evaporation method,and the optimal formulation was screened by Box-Behn...[Objectives]To prepare 20(S)-protopanaxadiol PLGA nanoparticles(20(S)-PPD-PLGA-NPs).[Methods]20(S)-PPD-PLGA-NPs were prepared by emulsion solvent evaporation method,and the optimal formulation was screened by Box-Behnken experiment with particle size and drug loading as the indicators through single factor experiment,and the drug release in vitro was carried out.[Results]The average diameter of the nanoparticles was(119.60±2.29)nm and the polydispersity index was(0.12±0.02),the size was uniform.The encapsulation efficiency and drug loading of protopanaxadiol were(87.99±1.29)%and(14.86±0.25)%,respectively.[Conclusions]The 20(S)-PPD-PLGA-NPs were successfully prepared by emulsion solvent evaporation method,and the 20(S)-PPD-PLGA-NPs had good stability,to lay a foundation for the study of 20(S)-PPD-PLGA-NPs in vitro and in vivo.展开更多
We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the“weaver”mouse,a model of progressive nigrostriatal degeneration.Here,we extended our...We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the“weaver”mouse,a model of progressive nigrostriatal degeneration.Here,we extended our investigation in two clinically-relevant ways.First,we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian donors.Second,we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice,at late stages of degeneration.We found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells,marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian donors.In agreement,we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver mice.However,the graft strongly induced an endogenous neurogenic response throughout the midbrain,which was significantly enhanced by the administration of microneurotrophin BNN-20.Our results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by BNN-20.Interestingly,the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.展开更多
文摘[Objectives]To prepare 20(S)-protopanaxadiol PLGA nanoparticles(20(S)-PPD-PLGA-NPs).[Methods]20(S)-PPD-PLGA-NPs were prepared by emulsion solvent evaporation method,and the optimal formulation was screened by Box-Behnken experiment with particle size and drug loading as the indicators through single factor experiment,and the drug release in vitro was carried out.[Results]The average diameter of the nanoparticles was(119.60±2.29)nm and the polydispersity index was(0.12±0.02),the size was uniform.The encapsulation efficiency and drug loading of protopanaxadiol were(87.99±1.29)%and(14.86±0.25)%,respectively.[Conclusions]The 20(S)-PPD-PLGA-NPs were successfully prepared by emulsion solvent evaporation method,and the 20(S)-PPD-PLGA-NPs had good stability,to lay a foundation for the study of 20(S)-PPD-PLGA-NPs in vitro and in vivo.
基金co-financed by Greece and the European Union(European Social Fund-ESF)through the Operational Programme《Human Resources Development,Education and Lifelong Learning 2014–2020》in the context of the project“NeuroProPar”(MIS 5047138,to IK)。
文摘We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the“weaver”mouse,a model of progressive nigrostriatal degeneration.Here,we extended our investigation in two clinically-relevant ways.First,we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian donors.Second,we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice,at late stages of degeneration.We found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells,marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian donors.In agreement,we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver mice.However,the graft strongly induced an endogenous neurogenic response throughout the midbrain,which was significantly enhanced by the administration of microneurotrophin BNN-20.Our results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by BNN-20.Interestingly,the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.