Guest editors:Prof.Zhonggao Gao,Institute of Materia Medica,Beijing,China Prof.Han Chang Kang,The Catholic University of Korea,Bucheon,Republic of Korea Article deadline:15 December 2015Publishing date:25 March 2016In...Guest editors:Prof.Zhonggao Gao,Institute of Materia Medica,Beijing,China Prof.Han Chang Kang,The Catholic University of Korea,Bucheon,Republic of Korea Article deadline:15 December 2015Publishing date:25 March 2016In this special issue of Functional Materials,Nanocarriers,and Formulations for Targeted Therapy。展开更多
D-a-Tocopheryl polyethylene glycol 1000 succinate(TPGS,also known as vitamin E-TPGS)is a biodegradable amphiphilic polymer prepared by esterification of vitamin E with polyethylene glycol(PEG)1000.It is approved by th...D-a-Tocopheryl polyethylene glycol 1000 succinate(TPGS,also known as vitamin E-TPGS)is a biodegradable amphiphilic polymer prepared by esterification of vitamin E with polyethylene glycol(PEG)1000.It is approved by the US Food and Drug Administration(FDA)and has found wide application in nanocarrier drug delivery systems(NDDS).Fully characterizing the in vivo fate and pharmacokinetic behavior of TPGS is important to promote the further development of TPGS-based NDDS.However,to date,a bioassay for the simultaneous quantitation of TPGS and its metabolite,PEG1000,has not been reported.In the present study,we developed such an innovative bioassay and used it to investigate the pharmacokinetics,tissue distribution and excretion of TPGS and PEG1000 in rat after oral and intravenous dosing.In addition,we evaluated the interaction of TPGS with cytochromes P450(CYP450s)in human liver microsomes.The results show that TPGS is poorly absorbed after oral administration with very low bioavailability and that,after intravenous administration,TPGS and PEG1000 are mainly distributed to the spleen,liver,lung and kidney before both being slowly eliminated in urine and feces as PEG1000.In vitro studies show the inhibition of human CYP450 enzymes by TPGS is limited to a weak inhibition of CYP3A4.Overall,our results provide a clear picture of the in vivo fate of TPGS which will be useful in evaluating the safety of TPGS-based NDDS in clinical use and in promoting their further development.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
文摘Guest editors:Prof.Zhonggao Gao,Institute of Materia Medica,Beijing,China Prof.Han Chang Kang,The Catholic University of Korea,Bucheon,Republic of Korea Article deadline:15 December 2015Publishing date:25 March 2016In this special issue of Functional Materials,Nanocarriers,and Formulations for Targeted Therapy。
基金supported by the National Natural Science Foundation of China(Grant Nos.81872831 and 82030107)the National Science and Technology Major Projects for‘significant new drugs creation’of the 13th five-year plan(2017ZX09101001 and 2018ZX09721002007,China)。
文摘D-a-Tocopheryl polyethylene glycol 1000 succinate(TPGS,also known as vitamin E-TPGS)is a biodegradable amphiphilic polymer prepared by esterification of vitamin E with polyethylene glycol(PEG)1000.It is approved by the US Food and Drug Administration(FDA)and has found wide application in nanocarrier drug delivery systems(NDDS).Fully characterizing the in vivo fate and pharmacokinetic behavior of TPGS is important to promote the further development of TPGS-based NDDS.However,to date,a bioassay for the simultaneous quantitation of TPGS and its metabolite,PEG1000,has not been reported.In the present study,we developed such an innovative bioassay and used it to investigate the pharmacokinetics,tissue distribution and excretion of TPGS and PEG1000 in rat after oral and intravenous dosing.In addition,we evaluated the interaction of TPGS with cytochromes P450(CYP450s)in human liver microsomes.The results show that TPGS is poorly absorbed after oral administration with very low bioavailability and that,after intravenous administration,TPGS and PEG1000 are mainly distributed to the spleen,liver,lung and kidney before both being slowly eliminated in urine and feces as PEG1000.In vitro studies show the inhibition of human CYP450 enzymes by TPGS is limited to a weak inhibition of CYP3A4.Overall,our results provide a clear picture of the in vivo fate of TPGS which will be useful in evaluating the safety of TPGS-based NDDS in clinical use and in promoting their further development.
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.