Significant investment in nanocarrier drug delivery systems(Nano-DDSs)has yielded only a limited number of successfully marketed nanomedicines,highlighting a low rate of clinical translation.A primary contributing fac...Significant investment in nanocarrier drug delivery systems(Nano-DDSs)has yielded only a limited number of successfully marketed nanomedicines,highlighting a low rate of clinical translation.A primary contributing factor is the lack of foundational understanding of in vivo processes.Comprehensive knowledge of the pharmacokinetics of Nano-DDSs is essential for developing more efficacious nanomedicines and accurately evaluating their safety and associated risks.However,the complexity of Nano-DDSs has impeded thorough and systematic pharmacokinetic studies.Key components of pharmacokinetic investigations on Nano-DDSs include the analysis of the released drug,the encapsulated drug,and the nanomaterial,which present a higher level of complexity compared to traditional small-molecule drugs.Establishing an appropriate approach for monitoring the pharmacokinetics of Nano-DDSs is crucial for facilitating the clinical translation of nanomedicines.This review provides an overview of advanced bioanalytical methodologies employed in studying the pharmacokinetics of anticancer organic Nano-DDSs over the past five years.We hope that this review will enhance the understanding of the pharmacokinetics of Nano-DDSs and support the advancement of nanomedicines.展开更多
Crossbreeding between Epinephelas coioides （ ♀ ） and Epinephelus lanceolatus （♂） was conducted by artificial insemination. Fertilized eggs were col- lected at 0, 30, 90 s, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,...Crossbreeding between Epinephelas coioides （ ♀ ） and Epinephelus lanceolatus （♂） was conducted by artificial insemination. Fertilized eggs were col- lected at 0, 30, 90 s, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 min post-insemination respectively, which were fixed by Smith＇s solution, embedded by paraffins and stained by H.E. According to the characteristics of Epinephelus coioides eggs, tissue section method was modified. The results showed that the sperms of Epinephelus lanceolatus rapidly entered the eggs of Epinephelus coioides at 30 s - 1 rain post-insemination. Observation results of tissue sections showed that mature eggs of Epinephelus coioides remained at metaphase of secondary maturation division. The eggs were activated after sperm penetration into the egg. With the develop- ment of secondary maturation division, at 2 rain post-insemination, eggs reached the metaphase of secondary maturation division ; at 3 - 6 rain post-insemination, sperm asters appeared; at 5 min post-insemination, eggs extruded secondary polar body; at 7 -15 rain post-insemination, male pronucleus and female pronucleus moved closer to each other and fused finally, forming a clear junction line; subsequently, zygote nucleus formed and karyotheca became faint; at 15 min pest-insem- ination, first karvokinetic division was develoued.展开更多
We propose a kind of second-order stabilized Crank-Nicolson schemewhich can be applied to three types of Cahn-Hilliard model with dynamic boundary conditions.We give the corresponding proof of stability and convergenc...We propose a kind of second-order stabilized Crank-Nicolson schemewhich can be applied to three types of Cahn-Hilliard model with dynamic boundary conditions.We give the corresponding proof of stability and convergence theoretically which takes the reaction rate dependent dynamic boundary conditions as an example.We verify the effectiveness and universality of our proposed scheme by conducting some typical numerical simulations and comparing with the literature works.It’s found that second-order scheme takes much less CPU time than the first-order scheme to reach the same final time.展开更多
Lead-free(Na_(0.5)Bi_(0.5))TiO_(3)-based dielectric materials are promising for electrostatic energy storage due to their strong polarization response and environmental friendliness.However,challenges like high electr...Lead-free(Na_(0.5)Bi_(0.5))TiO_(3)-based dielectric materials are promising for electrostatic energy storage due to their strong polarization response and environmental friendliness.However,challenges like high electric hysteresis loss(W_(loss))and low electric breakdown strength(Eb)limit their recoverable energy density(W_(rec))and energy conversion efficiency(η).A superparaelectric design with structure optimization has been proposed to overcome these restrictions.Based on this strategy,a series of(1-x)(Na_(0.3)Bi_(0.3)8Sr_(0.28))TiO3-xCa(Ta_(0.2)Ti_(0.75))O_(3)(abbreviated as(1-x)NBST-xCTT;x=0.0,0.1,0.2,0.3,and 0.4)ceramics were fabricated.Their phase structure gradually evolves from the rhombohedral and tetragonal coexistence(R&T)to the tetragonal and cubic coexistence(T&C),accompanied by the increasing proportion of weakly coupled and highly dynamic polar structures.This behavior enables the establishment of a superparaelectric relaxor ferroelectric(SPE-RFE)state,reducing Wloss,enhancingη,and improving dielectric stability.The improved microstructure with refined grains boosted Eb,further contributing to excellent performances.Notably,the optimized 0.6NBST-0.4CTT SPE-RFE ceramic,with high Eb,large polarization difference(ΔP),and slight Wloss,delivered a large Wrec of 6.90 J cm^(-3)with a highηof 92.55%at 600 kV cm^(-1),alongside excellent dielectric stability(-60 to 135℃)following the EIA-X7R standard.Moreover,a high power density(-125 MW cm^(-3))and an ultrafast charge-discharge rate(t_(0.9)∼33 ns)were realized at 300 kV cm-1.Encouragingly,the 0.6NBST-0.4CTT SPE-RFE ceramic also exhibits excellent energy-storage/charge-discharge stabilities.These results highlight the promising potential of the 0.6NBST-0.4CTT SPE-RFE ceramic for electrostatic energy storage.They also confirm the effectiveness of this strategy and provide valuable guidance for advancing dielectric energy-storage materials/capacitors.展开更多
Hydroxyethyl starch 130/0.4(HES130/0.4)is a macromolecular polysaccharide with polydispersity,which is widely used as a plasma expander.Full-profile bioanalysis of HES130/0.4 is required to characterize its plasma pha...Hydroxyethyl starch 130/0.4(HES130/0.4)is a macromolecular polysaccharide with polydispersity,which is widely used as a plasma expander.Full-profile bioanalysis of HES130/0.4 is required to characterize its plasma pharmacokinetics,yet current analytical technologies struggle with this task due to its complex structure and composition.To address this existing lacuna within the realm of analytical science,we propose a liquid chromatography-electrospray ionization mass spectrometry(LC-ESI-MS)methodology for the full-profile bioanalysis of HES130/0.4.Amide column separation with gradient optimization eluted polydisperse HES130/0.4 as a single symmetric peak.In-source collision-induced dissociation(IS-CID)converted the numerous precursor ions of HES130/0.4 into a limited number of characteristic fragment ions,from which m/z 597.4 was selected as the"pseudo-precursor ion"for MRM quantification.The ion transition m/z 597.4→435.3 was identified as the quantitative ion pair.The method demonstrated a linear calibration curve from 40μg/mL to 4000μg/L,with accuracy and precision meeting acceptance criteria,confirming its reliability and reproducibility.Subsequently,the workflow was successfully applied to investigate the pharmacokinetics of HES130/0.4 in rat,revealing its large distribution volume and rapid elimination within 24 h.This work provides a straightforward approach for the full-profile quantification of HES130/0.4 in biological samples,overcoming the limitations of traditional methods in terms of poor specificity,low sensitivity and narrow linear range,and providing a reference for the in vivo full-profile bioanalysis of HES130/0.4 and other polysaccharides.展开更多
Monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid)(PEG-PLA)is a typical amphiphilic di-block copolymer widely used as a nanoparticle carrier(nanocarrier)in drug delivery.Understanding the in vivo fate of PE...Monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid)(PEG-PLA)is a typical amphiphilic di-block copolymer widely used as a nanoparticle carrier(nanocarrier)in drug delivery.Understanding the in vivo fate of PEG-PLA is required to evaluate its overall safety and promote the development of PEG-PLA-based nanocarrier drug delivery systems.However,acquiring such understanding is limited by the lack of a suitable analytical method for the bioassay of PEG-PLA.In this study,the pharmacokinetics,biodistribution,metabolism and excretion of PEG-PLA were investigated in rat after intravenous administration.The results show that unchanged PEG-PLA is mainly distributed to spleen,liver,and kidney before being eliminated in urine over 48 h mainly(>80%)in the form of its PEG metabolite.Our study provides a clear and comprehensive picture of the in vivo fate of PEG-PLA which we anticipate will facilitate the scientifc design and safety evaluation of PEG-PLA-based nanocarrier drug delivery systems and thereby enhance their clinical development.展开更多
Because many therapeutic agents are contaminated by epimeric impurities or form epimers as a result of metabolism, analytical tools capable of determining epimers are increasingly in demand. This article is a proof-of...Because many therapeutic agents are contaminated by epimeric impurities or form epimers as a result of metabolism, analytical tools capable of determining epimers are increasingly in demand. This article is a proof-of-principle report of a novel DMS–MS/MS method to separate and simultaneously quantify epimers, taking PGF2α and its 8-epimer, 8-iso-PGF2α, as an example. Good accuracy and precision were achieved in the range of 10–500 ng/m L with a run time of only 1.5 min. Isopropanol as organic modifier facilitated a good combination of sensitivity and separation. The method is the first example of the quantitation of epimers without chromatographic separation.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.:82304443,82030107,and 82373944).
文摘Significant investment in nanocarrier drug delivery systems(Nano-DDSs)has yielded only a limited number of successfully marketed nanomedicines,highlighting a low rate of clinical translation.A primary contributing factor is the lack of foundational understanding of in vivo processes.Comprehensive knowledge of the pharmacokinetics of Nano-DDSs is essential for developing more efficacious nanomedicines and accurately evaluating their safety and associated risks.However,the complexity of Nano-DDSs has impeded thorough and systematic pharmacokinetic studies.Key components of pharmacokinetic investigations on Nano-DDSs include the analysis of the released drug,the encapsulated drug,and the nanomaterial,which present a higher level of complexity compared to traditional small-molecule drugs.Establishing an appropriate approach for monitoring the pharmacokinetics of Nano-DDSs is crucial for facilitating the clinical translation of nanomedicines.This review provides an overview of advanced bioanalytical methodologies employed in studying the pharmacokinetics of anticancer organic Nano-DDSs over the past five years.We hope that this review will enhance the understanding of the pharmacokinetics of Nano-DDSs and support the advancement of nanomedicines.
文摘Crossbreeding between Epinephelas coioides （ ♀ ） and Epinephelus lanceolatus （♂） was conducted by artificial insemination. Fertilized eggs were col- lected at 0, 30, 90 s, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 min post-insemination respectively, which were fixed by Smith＇s solution, embedded by paraffins and stained by H.E. According to the characteristics of Epinephelus coioides eggs, tissue section method was modified. The results showed that the sperms of Epinephelus lanceolatus rapidly entered the eggs of Epinephelus coioides at 30 s - 1 rain post-insemination. Observation results of tissue sections showed that mature eggs of Epinephelus coioides remained at metaphase of secondary maturation division. The eggs were activated after sperm penetration into the egg. With the develop- ment of secondary maturation division, at 2 rain post-insemination, eggs reached the metaphase of secondary maturation division ; at 3 - 6 rain post-insemination, sperm asters appeared; at 5 min post-insemination, eggs extruded secondary polar body; at 7 -15 rain post-insemination, male pronucleus and female pronucleus moved closer to each other and fused finally, forming a clear junction line; subsequently, zygote nucleus formed and karyotheca became faint; at 15 min pest-insem- ination, first karvokinetic division was develoued.
基金partially supported by the NSFC Nos.11871105 and 11231003partially supported by the NSFC No.12201050China Postdoctoral Science Foundation grant No.2022M710425.
文摘We propose a kind of second-order stabilized Crank-Nicolson schemewhich can be applied to three types of Cahn-Hilliard model with dynamic boundary conditions.We give the corresponding proof of stability and convergence theoretically which takes the reaction rate dependent dynamic boundary conditions as an example.We verify the effectiveness and universality of our proposed scheme by conducting some typical numerical simulations and comparing with the literature works.It’s found that second-order scheme takes much less CPU time than the first-order scheme to reach the same final time.
文摘Lead-free(Na_(0.5)Bi_(0.5))TiO_(3)-based dielectric materials are promising for electrostatic energy storage due to their strong polarization response and environmental friendliness.However,challenges like high electric hysteresis loss(W_(loss))and low electric breakdown strength(Eb)limit their recoverable energy density(W_(rec))and energy conversion efficiency(η).A superparaelectric design with structure optimization has been proposed to overcome these restrictions.Based on this strategy,a series of(1-x)(Na_(0.3)Bi_(0.3)8Sr_(0.28))TiO3-xCa(Ta_(0.2)Ti_(0.75))O_(3)(abbreviated as(1-x)NBST-xCTT;x=0.0,0.1,0.2,0.3,and 0.4)ceramics were fabricated.Their phase structure gradually evolves from the rhombohedral and tetragonal coexistence(R&T)to the tetragonal and cubic coexistence(T&C),accompanied by the increasing proportion of weakly coupled and highly dynamic polar structures.This behavior enables the establishment of a superparaelectric relaxor ferroelectric(SPE-RFE)state,reducing Wloss,enhancingη,and improving dielectric stability.The improved microstructure with refined grains boosted Eb,further contributing to excellent performances.Notably,the optimized 0.6NBST-0.4CTT SPE-RFE ceramic,with high Eb,large polarization difference(ΔP),and slight Wloss,delivered a large Wrec of 6.90 J cm^(-3)with a highηof 92.55%at 600 kV cm^(-1),alongside excellent dielectric stability(-60 to 135℃)following the EIA-X7R standard.Moreover,a high power density(-125 MW cm^(-3))and an ultrafast charge-discharge rate(t_(0.9)∼33 ns)were realized at 300 kV cm-1.Encouragingly,the 0.6NBST-0.4CTT SPE-RFE ceramic also exhibits excellent energy-storage/charge-discharge stabilities.These results highlight the promising potential of the 0.6NBST-0.4CTT SPE-RFE ceramic for electrostatic energy storage.They also confirm the effectiveness of this strategy and provide valuable guidance for advancing dielectric energy-storage materials/capacitors.
基金supported by the National Natural Science Foundation of China(Nos.82030107,82304443,82373944)。
文摘Hydroxyethyl starch 130/0.4(HES130/0.4)is a macromolecular polysaccharide with polydispersity,which is widely used as a plasma expander.Full-profile bioanalysis of HES130/0.4 is required to characterize its plasma pharmacokinetics,yet current analytical technologies struggle with this task due to its complex structure and composition.To address this existing lacuna within the realm of analytical science,we propose a liquid chromatography-electrospray ionization mass spectrometry(LC-ESI-MS)methodology for the full-profile bioanalysis of HES130/0.4.Amide column separation with gradient optimization eluted polydisperse HES130/0.4 as a single symmetric peak.In-source collision-induced dissociation(IS-CID)converted the numerous precursor ions of HES130/0.4 into a limited number of characteristic fragment ions,from which m/z 597.4 was selected as the"pseudo-precursor ion"for MRM quantification.The ion transition m/z 597.4→435.3 was identified as the quantitative ion pair.The method demonstrated a linear calibration curve from 40μg/mL to 4000μg/L,with accuracy and precision meeting acceptance criteria,confirming its reliability and reproducibility.Subsequently,the workflow was successfully applied to investigate the pharmacokinetics of HES130/0.4 in rat,revealing its large distribution volume and rapid elimination within 24 h.This work provides a straightforward approach for the full-profile quantification of HES130/0.4 in biological samples,overcoming the limitations of traditional methods in terms of poor specificity,low sensitivity and narrow linear range,and providing a reference for the in vivo full-profile bioanalysis of HES130/0.4 and other polysaccharides.
基金supported by the National Natural Science Foundation of China(Grant Nos.81872831 and 82030107)the National Science and Technology Major Projects for signifcant new drugs creation of the 13th fve-year plan(2017ZX09101001 and 2018ZX09721002007,China)。
文摘Monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid)(PEG-PLA)is a typical amphiphilic di-block copolymer widely used as a nanoparticle carrier(nanocarrier)in drug delivery.Understanding the in vivo fate of PEG-PLA is required to evaluate its overall safety and promote the development of PEG-PLA-based nanocarrier drug delivery systems.However,acquiring such understanding is limited by the lack of a suitable analytical method for the bioassay of PEG-PLA.In this study,the pharmacokinetics,biodistribution,metabolism and excretion of PEG-PLA were investigated in rat after intravenous administration.The results show that unchanged PEG-PLA is mainly distributed to spleen,liver,and kidney before being eliminated in urine over 48 h mainly(>80%)in the form of its PEG metabolite.Our study provides a clear and comprehensive picture of the in vivo fate of PEG-PLA which we anticipate will facilitate the scientifc design and safety evaluation of PEG-PLA-based nanocarrier drug delivery systems and thereby enhance their clinical development.
基金supported by the National Natural Science Foundation of China(Grant Nos.81430087 and 81673396)
文摘Because many therapeutic agents are contaminated by epimeric impurities or form epimers as a result of metabolism, analytical tools capable of determining epimers are increasingly in demand. This article is a proof-of-principle report of a novel DMS–MS/MS method to separate and simultaneously quantify epimers, taking PGF2α and its 8-epimer, 8-iso-PGF2α, as an example. Good accuracy and precision were achieved in the range of 10–500 ng/m L with a run time of only 1.5 min. Isopropanol as organic modifier facilitated a good combination of sensitivity and separation. The method is the first example of the quantitation of epimers without chromatographic separation.
