The shapes of particles and their distribution in tablets, controlled by pretreatment and tableting process, determine the pharmaceutical performance of excipient like lubricant. This study aims to provide deeper insi...The shapes of particles and their distribution in tablets, controlled by pretreatment and tableting process, determine the pharmaceutical performance of excipient like lubricant. This study aims to provide deeper insights to the relationship of the morphology and spatial distribution of stearic acid(SA) with the lubrication efficiency, as well as the resulting tablet property. Unmodified SA particles as flat sheet-like particles were firstly reprocessed by emulsification in hot water to obtain the reprocessed SA particles with spherical morphology. The three-dimensional(3 D) information of SA particles in tablets was detected by a quantitative and non-invasive 3 D structure elucidation technique, namely, synchrotron radiation X-ray micro-computed tomography(SR-μCT). SA particles in glipizide tablets prepared by using unmodified SA(GUT), reprocessed SA(GRT), as well as reference listed drug(RLD) of glipizide tablets were analyzed by SR-μCT. The results showed that the reprocessed SA with better flowability contributed to similarity of breaking forces between that of GRT and RLD. SA particles in GRT were very similar to those in RLD with uniform morphology and particle size, while SA particles in GUT were not evenly distributed. These findings not only demonstrated the feasibility of SR-μCT as a new method in revealing the morphology and spatial distribution of excipient in drug delivery system, but also deepened insights of solid dosage form design into a new scale by powder engineering.展开更多
The SeDeM Expert System was first known as a galenic pre-formulation system, which was based on the experimental research and quantitative determination of powdered substances. And the mathematical formula provided by...The SeDeM Expert System was first known as a galenic pre-formulation system, which was based on the experimental research and quantitative determination of powdered substances. And the mathematical formula provided by the SeDeM Expert System has plays an important role in the study of powder properties. The system can be used not only to evaluate the powder direct compression (DC) of excipients and active pharmaceutical ingredients (API’s), but also to predict the possible formulations, so it can reduce unnecessary research and trials, and shorten the time of development. In this paper, the research development and application of SeDeM Expert System in DC was summarized, and the results showed that with a few exceptions, the system was skilled in predicting acceptable tablet formulations. Finally, the new application prospect of the system is presented, including the application of the Internet traffic and content management (iTCM) database and the new co-processed excipients.展开更多
Tumor metastasis depends on the dynamic balance of the actomyosin cytoskeleton.As a key component of actomyosin filaments,non-muscle myosin-ⅡA disassembly contributes to tumor cell spreading and migration.However,its...Tumor metastasis depends on the dynamic balance of the actomyosin cytoskeleton.As a key component of actomyosin filaments,non-muscle myosin-ⅡA disassembly contributes to tumor cell spreading and migration.However,its regulatory mechanism in tumor migration and invasion is poorly understood.Here,we found that oncoprotein hepatitis B X-interacting protein(HBXIP) blocked the myosin-ⅡA assemble state promoting breast cancer cell migration.Mechanistically,mass spectrometry analysis,co-immunoprecipitation assay and GST-pull down assay proved that HBXIP directly interacted with the assembly-competent domain(ACD) of non-muscle heavy chain myosin-ⅡA(NMHC-ⅡA).The interaction was enhanced by NMHC-ⅡA S1916 phosphorylation via HBXIP-recruited protein kinase PKCβⅡ.Moreover,HBXIP induced the transcription of PRKCB,encoding PKCβⅡ,by coactivating Sp1,and triggered PKCβⅡ kinase activity.Interestingly,RNA sequencing and mouse metastasis model indicated that the anti-hyperlipidemic drug bezafibrate(BZF) suppressed breast cancer metastasis via inhibiting PKCβⅡ-mediated NMHC-ⅡA phosphorylation in vitro and in vivo.We reveal a novel mechanism by which HBXIP promotes myosin-ⅡA disassembly via interacting and phosphorylating NMHC-ⅡA,and BZF can serve as an effective anti-metastatic drug in breast cancer.展开更多
Metal-organic frameworks(MOFs),comprised of organic ligands and metal ions/metal clusters via coordinative bonds are highly porous,crystalline materials.Their tunable porosity,chemical composition,size and shape,and e...Metal-organic frameworks(MOFs),comprised of organic ligands and metal ions/metal clusters via coordinative bonds are highly porous,crystalline materials.Their tunable porosity,chemical composition,size and shape,and easy surface functionalization make this large family more and more popular for drug delivery.There is a growing interest over the last decades in the design of engineered MOFs with controlled sizes for a variety of biomedical applications.This article presents an overall review and perspectives of MOFs-based drug delivery systems(DDSs),starting with the MOFs classification adapted for DDSs based on the types of constituting metals and ligands.Then,the synthesis and characterization of MOFs for DDSs are developed,followed by the drug loading strategies,applications,biopharmaceutics and quality control.Importantly,a variety of representative applications of MOFs are detailed from a point of view of applications in pharmaceutics,diseases therapy and advanced DDSs.In particular,the biopharmaceutics and quality control of MOFs-based DDSs are summarized with critical issues to be addressed.Finally,challenges in MOFs development for DDSs are discussed,such as biostability,biosafety,biopharmaceutics and nomenclature.展开更多
有机锂离子电池技术作为新一代能源储备技术具有环境友好、理论容量高的优点,但也面临着活性材料溶于有机电解液的问题.本研究将高容量活性材料calix[4]quinone(C4Q)以不同比例(1:3–3:1)负载到有序介孔碳CMK-3中得到纳米复合材料C4Q/CM...有机锂离子电池技术作为新一代能源储备技术具有环境友好、理论容量高的优点,但也面临着活性材料溶于有机电解液的问题.本研究将高容量活性材料calix[4]quinone(C4Q)以不同比例(1:3–3:1)负载到有序介孔碳CMK-3中得到纳米复合材料C4Q/CMK-3,并通过XRD,SEM,TEM和BET实验手段对此复合材料进行了形貌和结构的表征.当C4Q在复合材料C4Q/CMK-3的比重为33.3%(1:2)时,其电化学性能表现最佳.首次循环放电容量为427 mA h g^(-1),经过100次循环后,放电容量保持率为58.7%.在大电流1 C充放电下,容量也能保持在170.4 mA h g^(-1).该研究结果证实了此优化方法可以用来改善有机材料的循环稳定性.展开更多
Polyethylene glycols(PEGs)in general use are polydisperse molecules with molecular weight(MW)distributed around an average value applied in their designation e.g.,PEG 4000.Previous research has shown that PEGs can act...Polyethylene glycols(PEGs)in general use are polydisperse molecules with molecular weight(MW)distributed around an average value applied in their designation e.g.,PEG 4000.Previous research has shown that PEGs can act as P-glycoprotein(P-gp)inhibitors with the potential to affect the absorption and efflux of concomitantly administered drugs.However,questions related to the mechanism of cellular uptake of PEGs and the exact role played by P-gp has not been addressed.In this study,we examined the mechanism of uptake of PEGs by MDCK-mock cells,in particular,the effect of MW and interaction with P-gp by MDCK-hMDRl and A549 cells.The results show that:(a)the uptake of PEGs by MDCK-hMDR1 cells is enhanced by P-gp inhibitors;(b)PEGs stimulate P-gp ATPase activity but to a much lesser extent than verapamil;and(c)uptake of PEGs of low MW(<2000 Da)occurs by passive diffusion whereas uptake of PEGs of hish MW(>5000 Da)occurs by a combination of passive diffusion and caveolae-mediated endocytosis.These findings suggest that PEGs can engage in P-gp-based drug interactions which we believe should be taken into account when using PEGs as excipients and in PEGylated drugs and drug delivery systems.展开更多
Changes in structure of oral solid dosage forms(OSDF) elementally determine the drug release and its therapeutic effects.In this research,synchrotron radiation X-ray micro-computed tomography was utilized to visualize...Changes in structure of oral solid dosage forms(OSDF) elementally determine the drug release and its therapeutic effects.In this research,synchrotron radiation X-ray micro-computed tomography was utilized to visualize the 3 D structure of enteric coated pellets recovered from the gastrointestinal tract of rats.The structures of pellets in solid state and in vitro compendium media were measured.Pellets in vivo underwent morphological and structural changes which differed significantly from those in vitro compendium media.Thus,optimizations of the dissolution media were performed to mimic the appropriate in vivo conditions by introducing pepsin and glass microspheres in media.The sphericity,pellet volume,pore volume and porosity of the in vivo esomeprazole magnesium pellets in stomach for2 h were recorded 0.47,1.55 × 10^(8)μm^(3),0.44 × 10^(8)μm^(3)and 27.6%,respectively.After adding pepsin and glass microspheres,the above parameters in vitro reached to 0.44,1.64 × 10^(8)μm^(3)0.38 × 10^(8)μm^(3)and 23.0%,respectively.Omeprazole magnesium pellets behaved similarly.The structural features of pellets between in vitro media and in vivo condition were bridged successfully in terms of 3 D structures to ensure better design,characterization and quality control of advanced OSDF.展开更多
Topological insulators are emergent states of quantum matter that are gapped in the bulk with timereversal symmetry-pteserved gapless edge/surface states, adiabatically distinct from conventional mat erials. By proxim...Topological insulators are emergent states of quantum matter that are gapped in the bulk with timereversal symmetry-pteserved gapless edge/surface states, adiabatically distinct from conventional mat erials. By proximity to various magnets and superconductors, to pological insula tors show novel physics at the interfaces, which give rise to two new areas named topological spintronics and topological quantum compu tat ion. Effects in the former such as the spin to rques, spin-charge conversion, to pological antiferromagnetic spintronics, and skyrmions realized in topological systems will be addressed. In the latter, a superconducting pairing gap leads to a state that supports Majorana fermions states, which may provide a new path for realizing to pological quantum comp ut at ion. Various signa tu res of Majorana zero modes/edge mode in topological superconductors will be discussed. The review ends by outlooks and potential applications of topological insulators. Topological superconductors that are fabricated using topological insulators with superconductors have a full pairing gap in the bulk and gapless surface states consisting of Majorana fermions. The theory of topological superconductors is reviewed, in close analogy to the theory of topological insulators.展开更多
基金The authors are grateful for the financial support from the National Science and Technology Major Project(2017ZX09101001-006)Thanks to the BL13W1 beamline of the SSRF for the precious beam time and help from the team.
文摘The shapes of particles and their distribution in tablets, controlled by pretreatment and tableting process, determine the pharmaceutical performance of excipient like lubricant. This study aims to provide deeper insights to the relationship of the morphology and spatial distribution of stearic acid(SA) with the lubrication efficiency, as well as the resulting tablet property. Unmodified SA particles as flat sheet-like particles were firstly reprocessed by emulsification in hot water to obtain the reprocessed SA particles with spherical morphology. The three-dimensional(3 D) information of SA particles in tablets was detected by a quantitative and non-invasive 3 D structure elucidation technique, namely, synchrotron radiation X-ray micro-computed tomography(SR-μCT). SA particles in glipizide tablets prepared by using unmodified SA(GUT), reprocessed SA(GRT), as well as reference listed drug(RLD) of glipizide tablets were analyzed by SR-μCT. The results showed that the reprocessed SA with better flowability contributed to similarity of breaking forces between that of GRT and RLD. SA particles in GRT were very similar to those in RLD with uniform morphology and particle size, while SA particles in GUT were not evenly distributed. These findings not only demonstrated the feasibility of SR-μCT as a new method in revealing the morphology and spatial distribution of excipient in drug delivery system, but also deepened insights of solid dosage form design into a new scale by powder engineering.
文摘The SeDeM Expert System was first known as a galenic pre-formulation system, which was based on the experimental research and quantitative determination of powdered substances. And the mathematical formula provided by the SeDeM Expert System has plays an important role in the study of powder properties. The system can be used not only to evaluate the powder direct compression (DC) of excipients and active pharmaceutical ingredients (API’s), but also to predict the possible formulations, so it can reduce unnecessary research and trials, and shorten the time of development. In this paper, the research development and application of SeDeM Expert System in DC was summarized, and the results showed that with a few exceptions, the system was skilled in predicting acceptable tablet formulations. Finally, the new application prospect of the system is presented, including the application of the Internet traffic and content management (iTCM) database and the new co-processed excipients.
基金supported by the grants from National Natural Science Foundation of China(82072929,82072943,and 31870752,China).
文摘Tumor metastasis depends on the dynamic balance of the actomyosin cytoskeleton.As a key component of actomyosin filaments,non-muscle myosin-ⅡA disassembly contributes to tumor cell spreading and migration.However,its regulatory mechanism in tumor migration and invasion is poorly understood.Here,we found that oncoprotein hepatitis B X-interacting protein(HBXIP) blocked the myosin-ⅡA assemble state promoting breast cancer cell migration.Mechanistically,mass spectrometry analysis,co-immunoprecipitation assay and GST-pull down assay proved that HBXIP directly interacted with the assembly-competent domain(ACD) of non-muscle heavy chain myosin-ⅡA(NMHC-ⅡA).The interaction was enhanced by NMHC-ⅡA S1916 phosphorylation via HBXIP-recruited protein kinase PKCβⅡ.Moreover,HBXIP induced the transcription of PRKCB,encoding PKCβⅡ,by coactivating Sp1,and triggered PKCβⅡ kinase activity.Interestingly,RNA sequencing and mouse metastasis model indicated that the anti-hyperlipidemic drug bezafibrate(BZF) suppressed breast cancer metastasis via inhibiting PKCβⅡ-mediated NMHC-ⅡA phosphorylation in vitro and in vivo.We reveal a novel mechanism by which HBXIP promotes myosin-ⅡA disassembly via interacting and phosphorylating NMHC-ⅡA,and BZF can serve as an effective anti-metastatic drug in breast cancer.
基金financially supported by the National Key R&D Program of China(No.2020YFE0201700)National Nature Science Foundation of China(No.81773645)a public grant overseen by the French National Research Agency(ANR),France as part of the“Investissements d’Avenir”program(Labex NanoSaclay:ANR-10-LABX-0035,France)
文摘Metal-organic frameworks(MOFs),comprised of organic ligands and metal ions/metal clusters via coordinative bonds are highly porous,crystalline materials.Their tunable porosity,chemical composition,size and shape,and easy surface functionalization make this large family more and more popular for drug delivery.There is a growing interest over the last decades in the design of engineered MOFs with controlled sizes for a variety of biomedical applications.This article presents an overall review and perspectives of MOFs-based drug delivery systems(DDSs),starting with the MOFs classification adapted for DDSs based on the types of constituting metals and ligands.Then,the synthesis and characterization of MOFs for DDSs are developed,followed by the drug loading strategies,applications,biopharmaceutics and quality control.Importantly,a variety of representative applications of MOFs are detailed from a point of view of applications in pharmaceutics,diseases therapy and advanced DDSs.In particular,the biopharmaceutics and quality control of MOFs-based DDSs are summarized with critical issues to be addressed.Finally,challenges in MOFs development for DDSs are discussed,such as biostability,biosafety,biopharmaceutics and nomenclature.
基金supported by the National Natural Science Foundation of China (21403187)the Natural Science Foundation of Hebei Province of China (B2015203124)the Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), Nankai University
文摘有机锂离子电池技术作为新一代能源储备技术具有环境友好、理论容量高的优点,但也面临着活性材料溶于有机电解液的问题.本研究将高容量活性材料calix[4]quinone(C4Q)以不同比例(1:3–3:1)负载到有序介孔碳CMK-3中得到纳米复合材料C4Q/CMK-3,并通过XRD,SEM,TEM和BET实验手段对此复合材料进行了形貌和结构的表征.当C4Q在复合材料C4Q/CMK-3的比重为33.3%(1:2)时,其电化学性能表现最佳.首次循环放电容量为427 mA h g^(-1),经过100次循环后,放电容量保持率为58.7%.在大电流1 C充放电下,容量也能保持在170.4 mA h g^(-1).该研究结果证实了此优化方法可以用来改善有机材料的循环稳定性.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.81430087,81673396,81872831 and 81603182)the National Science and Technology Major Projects for‘significant new drugs creation’of the 13th five-year plan(2017ZX09101001 and 2018ZX09721002007,China)
文摘Polyethylene glycols(PEGs)in general use are polydisperse molecules with molecular weight(MW)distributed around an average value applied in their designation e.g.,PEG 4000.Previous research has shown that PEGs can act as P-glycoprotein(P-gp)inhibitors with the potential to affect the absorption and efflux of concomitantly administered drugs.However,questions related to the mechanism of cellular uptake of PEGs and the exact role played by P-gp has not been addressed.In this study,we examined the mechanism of uptake of PEGs by MDCK-mock cells,in particular,the effect of MW and interaction with P-gp by MDCK-hMDRl and A549 cells.The results show that:(a)the uptake of PEGs by MDCK-hMDR1 cells is enhanced by P-gp inhibitors;(b)PEGs stimulate P-gp ATPase activity but to a much lesser extent than verapamil;and(c)uptake of PEGs of low MW(<2000 Da)occurs by passive diffusion whereas uptake of PEGs of hish MW(>5000 Da)occurs by a combination of passive diffusion and caveolae-mediated endocytosis.These findings suggest that PEGs can engage in P-gp-based drug interactions which we believe should be taken into account when using PEGs as excipients and in PEGylated drugs and drug delivery systems.
基金financial support from National Key R&D Program of China(2020YFE0201700)Major New Drugs Innovation and Development(2017ZX09101001-005,China)+1 种基金the National Natural Science Foundation of China(81803441,81803446 and 81773645)Youth Innovation Promotion Association CAS(2018323,China)。
文摘Changes in structure of oral solid dosage forms(OSDF) elementally determine the drug release and its therapeutic effects.In this research,synchrotron radiation X-ray micro-computed tomography was utilized to visualize the 3 D structure of enteric coated pellets recovered from the gastrointestinal tract of rats.The structures of pellets in solid state and in vitro compendium media were measured.Pellets in vivo underwent morphological and structural changes which differed significantly from those in vitro compendium media.Thus,optimizations of the dissolution media were performed to mimic the appropriate in vivo conditions by introducing pepsin and glass microspheres in media.The sphericity,pellet volume,pore volume and porosity of the in vivo esomeprazole magnesium pellets in stomach for2 h were recorded 0.47,1.55 × 10^(8)μm^(3),0.44 × 10^(8)μm^(3)and 27.6%,respectively.After adding pepsin and glass microspheres,the above parameters in vitro reached to 0.44,1.64 × 10^(8)μm^(3)0.38 × 10^(8)μm^(3)and 23.0%,respectively.Omeprazole magnesium pellets behaved similarly.The structural features of pellets between in vitro media and in vivo condition were bridged successfully in terms of 3 D structures to ensure better design,characterization and quality control of advanced OSDF.
基金the supports from the National Natural Science Foundation of China (Grant No.11874070)the National Key R&D Program of China (Grant No.2018YFA0305601)+1 种基金the Strategic Priority Research Program of Chinese Academy of Sciences (Grant No.XDB28000000)National Thousand-Young-Talents Program in China (Grant No.8206100161).
文摘Topological insulators are emergent states of quantum matter that are gapped in the bulk with timereversal symmetry-pteserved gapless edge/surface states, adiabatically distinct from conventional mat erials. By proximity to various magnets and superconductors, to pological insula tors show novel physics at the interfaces, which give rise to two new areas named topological spintronics and topological quantum compu tat ion. Effects in the former such as the spin to rques, spin-charge conversion, to pological antiferromagnetic spintronics, and skyrmions realized in topological systems will be addressed. In the latter, a superconducting pairing gap leads to a state that supports Majorana fermions states, which may provide a new path for realizing to pological quantum comp ut at ion. Various signa tu res of Majorana zero modes/edge mode in topological superconductors will be discussed. The review ends by outlooks and potential applications of topological insulators. Topological superconductors that are fabricated using topological insulators with superconductors have a full pairing gap in the bulk and gapless surface states consisting of Majorana fermions. The theory of topological superconductors is reviewed, in close analogy to the theory of topological insulators.