Exploring the potential to enhance drug distribution in the brain subregion via intranasal delivery of nanoemulsion in combination with borneol as a guider

The number of people with Alzheimer’s disease(AD)is increasing annually,with the nidus mainly concentrated in the cortex and hippocampus.Despite of numerous efforts,effective treatment of AD is still facing great challenges due to the blood brain barrier(BBB)and limited drug distribution in the AD nidus sites.Thus,in this study,using vinpocetine(VIN)as a model drug,the objective is to explore the feasibility of tackling the above bottleneck via intranasal drug delivery in combination with a brain guider,borneol(BOR),using nanoemulsion(NE)as the carrier.First of all,the NE were prepared and characterized.In vivo behavior of the NE after intranasal administration was investigated.Influence of BOR dose,BOR administration route on drug brain targeting behavior was evaluated,and the influence of BOR addition on drug brain subregion distribution was probed.It was demonstrated that all the NE had comparable size and similar retention behavior after intranasal delivery.Compared to intravenous injection,improved brain targeting effect was observed by intranasal route,and drug targeting index(DTI)of the VIN–NE group was 154.1%,with the nose-to-brain direct transport percentage(DTP)35.1%.Especially,remarkably enhanced brain distribution was achieved after BOR addition in the NE,with the extent depending on BOR dose.VIN brain concentration was the highest in the VIN-1-BOR-NE group at BOR dose of 1 mg/kg,with the DTI reaching 596.1%and the DTP increased to 83.1%.BOR could exert better nose to brain delivery when administrated together with the drug via intranasal route.Notably,BOR can remarkably enhance drug distribution in both hippocampus and cortex,the nidus areas of AD.In conclusion,in combination with intranasal delivery and the intrinsic brain guiding effect of BOR,drug distribution not only in the brain but also in the cortex and hippocampus can be enhanced significantly,providing the perquisite for improved therapeutic efficacy of AD.

Low temperature densification mechanism and properties of Ta_(1-x)Hf_(x)C solid solutions with decarbonization and phase transition of Cr_(3)C_(2)

As a novel member of the ultra-high temperature ceramic family,which have extremely high melting points and remarkable hardness,Ta1-xHfxC solid solution ceramics are promising for applications in thermal protection systems.Ta_(1-x)Hf_(x)C(x=0,0.2,0.5,0.8,and 1.0)with 2 vol%Cr_(3)C_(2),were densified up to 98.8%at 2000℃ using a two-step spark plasma sintering process.Effect of Cr_(3)C_(2) on the linear shrinkage of Ta1-xHfxC was investigated.Possible‘eutectic’reaction within TaCeCr_(3)C_(2) ceramic was inferred to contribute to the shrinkage at 1462 C.High-angle annular dark-field scanning transmission electron microscopy combined with energy-dispersive spectroscopy was employed to further confirm the mutual diffusion between rock-salt structured‘CrCx’and TaC.Flexural strength,fracture toughness and Vicker’s hardness of Ta1-xHfxC ceramics were in the range of 439e492 MPa,4.0e5.8 MPa∙m^(1/2) and 14.9e19.9 GPa respectively.The coefficient of thermal expansion(in the temperature range of 25e1000℃)and thermal conductivity(at 1000℃)of Ta_(1-x)Hf_(x)C varied from 7.17 to 7.51×10^(-6) K^(-1) and 31.9e42.9 W/m·K,respectively.The high-temperature strength of Ta_(0.5)Hf_(0.5)C decreased to 165 MPa up to 1600℃,approximately 34%of room-temperature strength,and a‘zig-zag’load-displacement curve was observed.

Assessing effects of reopening policies on COVID-19 pandemic in Texas with a data-driven transmission model

While the Coronavirus Disease 2019(COVID-19)pandemic continues to threaten public health and safety,every state has strategically reopened the business in the United States.It is urgent to evaluate the effect of reopening policies on the COVID-19 pandemic to help with the decision-making on the control measures and medical resource allocations.In this study,a novel SEIR model was developed to evaluate the effect of reopening policies based on the real-world reported COVID-19 data in Texas.The earlier reported data before the reopening were used to develop the SEIR model;data after the reopening were used for evaluation.The simulation results show that if continuing the“stay-at-home order”without reopening the business,the COVID-19 pandemic could end in December 2020 in Texas.On the other hand,the pandemic could be controlled similarly as the case of noreopening only if the contact rate was low and additional high magnitude of control measures could be implemented.If the control measures are only slightly enhanced after reopening,it could flatten the curve of the COVID-19 epidemic with reduced numbers of infections and deaths,but it might make the epidemic last longer.Based on the reported data up to July 2020 in Texas,the real-world epidemic pattern is between the cases of the low and high magnitude of control measures with a medium risk of contact rate after reopening.In this case,the pandemic might last until summer 2021 to February 2022 with a total of 4-10 million infected cases and 20,080e58,604 deaths.