Drug metabolism and pharmacokinetics(DMPK) is an important branch of pharmaceutical sciences.The nature of ADME(absorption,distribution,metabolism,excretion) and PK(pharmacokinetics) inquiries during drug discovery an...Drug metabolism and pharmacokinetics(DMPK) is an important branch of pharmaceutical sciences.The nature of ADME(absorption,distribution,metabolism,excretion) and PK(pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems.Tremendous progress has been made in the past decade,not only in the characterization of physiochemical properties of drugs that influence their ADME,target organ exposure,and toxicity,but also in the identification of design principles that can minimize drug-drug interaction(DDI) potentials and reduce the attritions.The importance of membrane transporters in drug disposition,efficacy,and safety,as well as the interplay with metabolic processes,has been increasingly recognized.Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs,such as peptides,oligonucleotides,and antibody-drug conjugates,necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties.In this review,we highlight some of the most notable advances in the last decade,and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.展开更多
As a promising new micro-physiological system,organ-on-a-chip has been widely utilized for in vitro pharmaceutical study and tissues engineering based on the three-dimensional constructions of tissues/organs and delic...As a promising new micro-physiological system,organ-on-a-chip has been widely utilized for in vitro pharmaceutical study and tissues engineering based on the three-dimensional constructions of tissues/organs and delicate replication of in vivo-like microenvironment.To better observe the biological processes,a variety of sensors have been integrated to realize in-situ,realtime,and sensitive monitoring of critical signals for organs development and disease modeling.Herein,we discuss the recent research advances made with respect to sensors-integrated organ-on-a-chip in this overall review.Firstly,we briefly explore the underlying fabrication procedures of sensors within microfluidic platforms and several classifications of sensory principles.Then,emphasis is put on the highlighted applications of different types of organ-on-a-chip incorporated with various sensors.Last but not least,perspective on the remaining challenges and future development of sensors-integrated organ-on-a-chip are presented.展开更多
基金supported in part by grants from the National Institutes of Health (CA023074,CA092596,ES004940,ES006694,and ES020867,USA)。
文摘Drug metabolism and pharmacokinetics(DMPK) is an important branch of pharmaceutical sciences.The nature of ADME(absorption,distribution,metabolism,excretion) and PK(pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems.Tremendous progress has been made in the past decade,not only in the characterization of physiochemical properties of drugs that influence their ADME,target organ exposure,and toxicity,but also in the identification of design principles that can minimize drug-drug interaction(DDI) potentials and reduce the attritions.The importance of membrane transporters in drug disposition,efficacy,and safety,as well as the interplay with metabolic processes,has been increasingly recognized.Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs,such as peptides,oligonucleotides,and antibody-drug conjugates,necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties.In this review,we highlight some of the most notable advances in the last decade,and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.
基金This work was supported by the National Key Research and Development Program of China(No.2020YFA0908200)the National Natural Science Foundation of China(Nos.T2225003,52073060,and 61927805)+2 种基金the Nanjing Medical Science and Technique Development Foundation(No.ZKX21019)the Guangdong Basic and Applied Basic Research Foundation(No.2021B1515120054)the Shenzhen Fundamental Research Program(Nos.JCYJ20190813152616459 and JCYJ20210324133214038)。
文摘As a promising new micro-physiological system,organ-on-a-chip has been widely utilized for in vitro pharmaceutical study and tissues engineering based on the three-dimensional constructions of tissues/organs and delicate replication of in vivo-like microenvironment.To better observe the biological processes,a variety of sensors have been integrated to realize in-situ,realtime,and sensitive monitoring of critical signals for organs development and disease modeling.Herein,we discuss the recent research advances made with respect to sensors-integrated organ-on-a-chip in this overall review.Firstly,we briefly explore the underlying fabrication procedures of sensors within microfluidic platforms and several classifications of sensory principles.Then,emphasis is put on the highlighted applications of different types of organ-on-a-chip incorporated with various sensors.Last but not least,perspective on the remaining challenges and future development of sensors-integrated organ-on-a-chip are presented.
