Objective:Transdermal drug delivery systems represent a critical focus in the pharmaceutics field;however,their use is limited by the fact that many drugs usually pass through the skin with low permeability.Menthol is...Objective:Transdermal drug delivery systems represent a critical focus in the pharmaceutics field;however,their use is limited by the fact that many drugs usually pass through the skin with low permeability.Menthol is a common penetration enhancer because of its high penetration-enhancing efficiency and safety.Our research aimed to reveal the penetrationenhancing mechanisms of menthol via a multiscale study.Methods:First,the interaction of menthol with the stratum corneum was studied using vertical Franz diffusion cells obtained from the abdominal skin of rats as a model.Then,the skin samples were observed via transmission electron microscopy.Finally,the interaction of different concentrations of menthol with a mixed lipid model of the stratum corneum was investigated via molecular dynamics simulation using the GROMOS 54A7 force field on a microcosmic level.Results:At concentrations of 3.5%or lower,menthol changed the original structure of the stratum corneum to varying degrees,which increased its fluidity and facilitated the permeation and storage of menthol.Menthol increased the fluidity of the stratum corneum mainly via two mechanisms.First,menthol had strong hydrogen-bonding capability,and it could compete for the lipidelipid hydrogen bonding sites,thereby weakening the stability of the hydrogenbonding network connecting the skin lipids.In addition,menthol had strong affinity for cholesterol,probably due to their similar molecular structures,suggesting that the incorporation of menthol would increase the fluidity of the lipid membrane similarly to cholesterol.Conclusion:The penetration-enhancing mechanism of menthol was explained using in vitro and molecular dynamics simulation methods.These findings may advance the basic research of transdermal drug delivery systems and facilitate the discoveries of novel penetration enhancers.展开更多
Objective:To study the transmembrane transport of chemical components of Chinese herbs and to explore the function of platycodin D (PD) on biomembranes.Methods:Interaction between PD and the dipalmitoylphosphatidylcho...Objective:To study the transmembrane transport of chemical components of Chinese herbs and to explore the function of platycodin D (PD) on biomembranes.Methods:Interaction between PD and the dipalmitoylphosphatidylcholine (DPPC) bilayer was reproduced by molecular dynamics simulation with the Martini force field.A model validation and methodological study were first performed,and were based on simulation investigations of transmembrane transport for three herbal compounds with distinct hydrophilic properties.Results:PD increased the mobility of the DPPC bilayer since its aglycone strongly interacted with the hydrophobic layer,which broke the structure of the gate layer,and weakened the ordered performance of hydrophobic tails.Conclusion:The Martini force field was successfully applied to the study of the interaction between herbal compounds and a biological membrane.By combining the dynamics equilibrium morphology,the distribution of drugs inside and outside the biomembrane,and the interaction sites of drugs on the DPPC bilayer,factors influencing transmembrane transport of drugs were elucidated and the function of platycodin D in a biological membrane was reproduced.展开更多
Polyphenols are widely recognized as the effective antioxidants,which are divided into flavonoids,phenolic acids,stilbenes,lignans,tannins and so on.They could regulate internal functions and protect the body from dis...Polyphenols are widely recognized as the effective antioxidants,which are divided into flavonoids,phenolic acids,stilbenes,lignans,tannins and so on.They could regulate internal functions and protect the body from diseases related to oxidative damage.Due to the fact that their antioxidant capacity is influenced by the structure,stability and bioavailability,the detection of their bioactivity should be considered comprehensively.Currently,the methods for measuring the antioxidant capacity of phenolic compounds are divided into chemical,cell-based and in vivo assays.The chemical assays include 2,2-diphenyl-l-picrylhydrazyl(DPPHI),2,2"-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),ferric reducing/antioxidant power(FRAP),oxygen radical absorbance capacity(ORAC),peroxyI radical scavenging capacity(PSC),which are rapid identification method,but their reaction mechanism has a great gap with the internal body response.The cell-based assays are more consistent with biological reaction,but still do not take the bioavailability into consideration.The in vivo assays,which commonly utilized Caenorhabditis elegans or rats as models,are more representative,but these methods are more complex and spend longer.This review summarizes the antioxidant evaluation methods of phenolic compounds and discusses their advantages and limitations comparatively,which could help discriminate and select the appropriate assay in the actual operation,and facilitate the development of comprehensive approaches as well.展开更多
The study aims to identify the potential acute effects of suspended aluminum nitride（Al N）nanoparticles（NPs） on soluble microbial products（SMP） of activated sludge.Cultured activated sludge loaded with 1,10,50,1...The study aims to identify the potential acute effects of suspended aluminum nitride（Al N）nanoparticles（NPs） on soluble microbial products（SMP） of activated sludge.Cultured activated sludge loaded with 1,10,50,100,150 and 200 mg/L of Al N NPs were carried out in this study.As results showed,Al N NPs had a highly inverse proportionality to bacterial dehydrogenase and OUR,indicating its direct toxicity to the activated sludge viability.The toxicity of Al N NPs was mainly due to the nano-scale of Al N NPs.In SMP,Al N NPs led to the decrease of polysaccharide and humic compounds,but had slight effects on protein.The decrease of tryptophan-like substances in SMP indicated the inhibition of Al N NPs on the bacterial metabolism.Additionally,Al N NPs reduced obviously the molecular weight of SMP,which might be due to the nano-scale of Al N.展开更多
基金This work was supported by the Municipal Natural Science Foundation of Beijing(7162122).
文摘Objective:Transdermal drug delivery systems represent a critical focus in the pharmaceutics field;however,their use is limited by the fact that many drugs usually pass through the skin with low permeability.Menthol is a common penetration enhancer because of its high penetration-enhancing efficiency and safety.Our research aimed to reveal the penetrationenhancing mechanisms of menthol via a multiscale study.Methods:First,the interaction of menthol with the stratum corneum was studied using vertical Franz diffusion cells obtained from the abdominal skin of rats as a model.Then,the skin samples were observed via transmission electron microscopy.Finally,the interaction of different concentrations of menthol with a mixed lipid model of the stratum corneum was investigated via molecular dynamics simulation using the GROMOS 54A7 force field on a microcosmic level.Results:At concentrations of 3.5%or lower,menthol changed the original structure of the stratum corneum to varying degrees,which increased its fluidity and facilitated the permeation and storage of menthol.Menthol increased the fluidity of the stratum corneum mainly via two mechanisms.First,menthol had strong hydrogen-bonding capability,and it could compete for the lipidelipid hydrogen bonding sites,thereby weakening the stability of the hydrogenbonding network connecting the skin lipids.In addition,menthol had strong affinity for cholesterol,probably due to their similar molecular structures,suggesting that the incorporation of menthol would increase the fluidity of the lipid membrane similarly to cholesterol.Conclusion:The penetration-enhancing mechanism of menthol was explained using in vitro and molecular dynamics simulation methods.These findings may advance the basic research of transdermal drug delivery systems and facilitate the discoveries of novel penetration enhancers.
基金The experiment was financially supported by the National Natural Science Foundation of China(81473364)Beijing Natural Science Foundation(7162122)Excellent Talents Training Subsidy Scheme of Beijing(2013D009999000003).
文摘Objective:To study the transmembrane transport of chemical components of Chinese herbs and to explore the function of platycodin D (PD) on biomembranes.Methods:Interaction between PD and the dipalmitoylphosphatidylcholine (DPPC) bilayer was reproduced by molecular dynamics simulation with the Martini force field.A model validation and methodological study were first performed,and were based on simulation investigations of transmembrane transport for three herbal compounds with distinct hydrophilic properties.Results:PD increased the mobility of the DPPC bilayer since its aglycone strongly interacted with the hydrophobic layer,which broke the structure of the gate layer,and weakened the ordered performance of hydrophobic tails.Conclusion:The Martini force field was successfully applied to the study of the interaction between herbal compounds and a biological membrane.By combining the dynamics equilibrium morphology,the distribution of drugs inside and outside the biomembrane,and the interaction sites of drugs on the DPPC bilayer,factors influencing transmembrane transport of drugs were elucidated and the function of platycodin D in a biological membrane was reproduced.
基金supported by the National Key Research and Development Plan for the Fourteenth Five Year(2022YFD2100803)the National Natural Science Foundation of China(32202040)+1 种基金the First Batch of Liaoning“Unveiling Leader”Scientific and Technological Projects(2021JH1/10400036)the Key Laboratory of Marine Fishery Resources Exploitment&Utilization of Zhejiang Province(SL2022015).
文摘Polyphenols are widely recognized as the effective antioxidants,which are divided into flavonoids,phenolic acids,stilbenes,lignans,tannins and so on.They could regulate internal functions and protect the body from diseases related to oxidative damage.Due to the fact that their antioxidant capacity is influenced by the structure,stability and bioavailability,the detection of their bioactivity should be considered comprehensively.Currently,the methods for measuring the antioxidant capacity of phenolic compounds are divided into chemical,cell-based and in vivo assays.The chemical assays include 2,2-diphenyl-l-picrylhydrazyl(DPPHI),2,2"-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),ferric reducing/antioxidant power(FRAP),oxygen radical absorbance capacity(ORAC),peroxyI radical scavenging capacity(PSC),which are rapid identification method,but their reaction mechanism has a great gap with the internal body response.The cell-based assays are more consistent with biological reaction,but still do not take the bioavailability into consideration.The in vivo assays,which commonly utilized Caenorhabditis elegans or rats as models,are more representative,but these methods are more complex and spend longer.This review summarizes the antioxidant evaluation methods of phenolic compounds and discusses their advantages and limitations comparatively,which could help discriminate and select the appropriate assay in the actual operation,and facilitate the development of comprehensive approaches as well.
基金supported by the National Natural Science Foundation of China(No.51378368)the Foundation of State Key Laboratory of Pollution Control and Resource Reuse(Tongji University),China(No.PCRRT16003)Shenzhen Science and Technology Research Fund(No.CXZZ20150330151321966)
文摘The study aims to identify the potential acute effects of suspended aluminum nitride（Al N）nanoparticles（NPs） on soluble microbial products（SMP） of activated sludge.Cultured activated sludge loaded with 1,10,50,100,150 and 200 mg/L of Al N NPs were carried out in this study.As results showed,Al N NPs had a highly inverse proportionality to bacterial dehydrogenase and OUR,indicating its direct toxicity to the activated sludge viability.The toxicity of Al N NPs was mainly due to the nano-scale of Al N NPs.In SMP,Al N NPs led to the decrease of polysaccharide and humic compounds,but had slight effects on protein.The decrease of tryptophan-like substances in SMP indicated the inhibition of Al N NPs on the bacterial metabolism.Additionally,Al N NPs reduced obviously the molecular weight of SMP,which might be due to the nano-scale of Al N.
