Poly(ethylene glycol)-poly(n-butyl cyanoacrylate)(PEG-PBCA)is a remarkable drug delivery carrier for permeating blood-brain barrier.In this work,a novel high-gravity procedure was reported to intensify Knoevenagel con...Poly(ethylene glycol)-poly(n-butyl cyanoacrylate)(PEG-PBCA)is a remarkable drug delivery carrier for permeating blood-brain barrier.In this work,a novel high-gravity procedure was reported to intensify Knoevenagel condensation-Michael addition polymerization of PEG-PBCA.A series of PEG-PBCA containing different block ratios were synthesized with narrow molecular weight distribution of polydispersity indexes less than 1.1.Furthermore,the reaction time reduced 60%compared to conventional stirred tank reactor process.Chemical structures of as-prepared polymers were characterized.In vitro drug delivery performance was evaluated.The cytotoxicity of PEG-PBCA to brain microvessel endothelial cells(BMVEC)decreases with the extension of the PEG chain and the shortening of the PBCA chain.The polymer cellular uptake to BMVECs was better after improving hydrophilicity by PEG block.Results of bloodbrain barrier permeability demonstrated that medium length of PBCA chain and short PEG chain are favorable for hydrophobic Nile red permeation,while long PEG chain and short PBCA chain are beneficial to delivery water-soluble doxorubicin hydrochloride(Dox).The average apparent permeability coeffi-cient increased 1.7 and 0.25 times than that of raw Nile red and Dox,respectively.High-gravity intensi-fied condensation polymerization should have great potential in brain drug delivery system.展开更多
Contact tracing is an important public health measure to control disease transmission.However,it is difficult to assess contact tracing during the exponential stage of an epidemic with multiple control measures,becaus...Contact tracing is an important public health measure to control disease transmission.However,it is difficult to assess contact tracing during the exponential stage of an epidemic with multiple control measures,because the exponential growth rate is influenced by all measures.We present new SEIR and SEAIR contact tracing models that track contacts in randomly mixed populations,and calibrate them to simulated epidemic curves to determine the data that allow us to assess the effect of contact tracing.We find that new-case counts,counts of cases identified by contact tracing(or voluntary tests),and counts of symptomatic onset are necessary to identify model parameters and evaluate the effect of contact tracing.We fit our contact tracing models to COVID-19 pandemic data in Ontario,Canada,during March 16eMay 1,2020.Our results show that approximately 29%of cases were identified via contact tracing of close contacts.Contact tracing moderately reduces the control reproduction number by about 25%,but significantly reduces the prevalence by more than half.Ignoring asymptomatic transmissions gives similar estimates for the effect of contact tracing,but significantly underestimates the prevalence.展开更多
基金This work was supported by National Key Research and Development Program of China(2016YFA0201701).
文摘Poly(ethylene glycol)-poly(n-butyl cyanoacrylate)(PEG-PBCA)is a remarkable drug delivery carrier for permeating blood-brain barrier.In this work,a novel high-gravity procedure was reported to intensify Knoevenagel condensation-Michael addition polymerization of PEG-PBCA.A series of PEG-PBCA containing different block ratios were synthesized with narrow molecular weight distribution of polydispersity indexes less than 1.1.Furthermore,the reaction time reduced 60%compared to conventional stirred tank reactor process.Chemical structures of as-prepared polymers were characterized.In vitro drug delivery performance was evaluated.The cytotoxicity of PEG-PBCA to brain microvessel endothelial cells(BMVEC)decreases with the extension of the PEG chain and the shortening of the PBCA chain.The polymer cellular uptake to BMVECs was better after improving hydrophilicity by PEG block.Results of bloodbrain barrier permeability demonstrated that medium length of PBCA chain and short PEG chain are favorable for hydrophobic Nile red permeation,while long PEG chain and short PBCA chain are beneficial to delivery water-soluble doxorubicin hydrochloride(Dox).The average apparent permeability coeffi-cient increased 1.7 and 0.25 times than that of raw Nile red and Dox,respectively.High-gravity intensi-fied condensation polymerization should have great potential in brain drug delivery system.
基金funded by:Michael Smith Foundation for Health Research and the Victoria Hospitals Foundation(LC:COV2020-1061)Natural Sciences and Engineering Research Council(NSERC)Discovery Grants(LC:RGPIN-2013-327025,JM:RGPIN-03789-2018,PvdD:RGPIN-2016-03677)NSERC Emerging Infectious Diseases Modelling Initiative grants(LC:RGPID-560514-2020,JM:RGPID-560523-2020,RGPID-560520-2020).
文摘Contact tracing is an important public health measure to control disease transmission.However,it is difficult to assess contact tracing during the exponential stage of an epidemic with multiple control measures,because the exponential growth rate is influenced by all measures.We present new SEIR and SEAIR contact tracing models that track contacts in randomly mixed populations,and calibrate them to simulated epidemic curves to determine the data that allow us to assess the effect of contact tracing.We find that new-case counts,counts of cases identified by contact tracing(or voluntary tests),and counts of symptomatic onset are necessary to identify model parameters and evaluate the effect of contact tracing.We fit our contact tracing models to COVID-19 pandemic data in Ontario,Canada,during March 16eMay 1,2020.Our results show that approximately 29%of cases were identified via contact tracing of close contacts.Contact tracing moderately reduces the control reproduction number by about 25%,but significantly reduces the prevalence by more than half.Ignoring asymptomatic transmissions gives similar estimates for the effect of contact tracing,but significantly underestimates the prevalence.
