Reducing systemic absorption and macrophages clearance of genistein by lipid-coated nanocrystals for pulmonary delivery

Pulmonary delivery is an effective drug delivery strategy for the treatment of local respiratory diseases.However,the rapid systemic absorption through the lung due to the thin barrier and persistent lung clearances influence the drug retention in the lung.In this study,we designed a lipid-coated genistein nanocrystals(Lipo-NCs)formulation to achieve enhanced efficiency of local pulmonary delivery.The LipoNCs were fabricated by modifying genistein nanocrystals(NCs)with phospholipid membrane through thin film hydration following the homogenization method.The prepared Lipo-NCs exhibited a decreased drug release rate compared with the naked NCs.Our results demonstrated that intracellular uptake and transcellular transport of NCs by the Calu-3 epithelial layer were reduced after lipid coating.Furthermore,the macrophages clearance was also impeded by this Lipo-NCs formulation.In vivo lung retention and distribution revealed that more genistein was retained in the lung after intratracheal administration of Lipo-NCs.The pharmacokinetic study displayed that the AUC((0-t))values of Lipo-NCs were 1.59-fold lesser than those of the NCs group,indicating a reduced systemic absorption.In conclusion,this research indicated that Lipo-NCs could be a suitable formulation for reducing systemic absorption and macrophages clearance,and thus enhancing drug concentration in lung by pulmonary delivery.

Effects of subsoiling on working quality and total power consumption of high stubble straw returning machine

Straw returning into field is a direct and effective measure to reduce the straw burning and improve the soil organic matter content.Straw returning directly to field needs higher performance machines,especially under the condition of large amount of straw in the field is more difficult.Therefore,the model of conservation tillage by combination of subsoiling and straw returning was studied.Experiments on combined tillage machine for effect of subsoiling on working quality and total power consumption for high stubble straw returning were carried out.The high stubble rape field was used as the test field;forward speed and PTO speed of tractor were taken as the test factors.Straw coverage rate and straw proportion of the lower half burying layer were taken as the test indexes of the working quality.Subsoiling and rotary burying(SRB)returning operation was used as experimental group and direct rotary burying(DRB)returning operation was the control group.The results showed that under different working conditions,the mean value of straw coverage rate of SRB was 93.0%,straw proportion of the lower half burying layer was 52.8%,these values were better than DRB.The straw proportion of the lower half burying layer of SRB compared with DRB increased by 10.5%.Two factors all had a significant effect on it under the SRB and DRB conditions.Subsoiling could significantly reduce the PTO torque.Under low speed,the total power consumption of SRB was slightly smaller,while under high speed,the total power consumption of DRB was slightly smaller.Under the SRB and DRB conditions,two factors both had a significant effect on total power consumption.The optimal working combination(working quality as the primary index)was 1.5 km/h of forward speed and 720 r/min of PTO speed.Under this condition,the straw coverage rate was 94.1%,the straw proportion of the lower half burying layer was 59.0%,and the total power consumption was 35.62 kW.The research confirmed that subsoiling is beneficial to the working quality and total power consumption of high stubble straw returning machine.It could meet the working requirements,and provide a reference for optimizing straw returning machine and improving working quality.