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
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
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
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.
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.
