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
采用高碘酸氧化-还原胺化法对尿酸酶的N端氨基进行聚乙二醇修饰研究。首先,以相对分子质量为20 k D的单甲氧基聚乙二醇氨基盐酸盐(m PEG20000-NH2·HCl)和N-叔丁氧羰基-L-丝氨酸(Boc-Ser-OH)为原料通过酰胺化反应制备聚乙二醇中间体...采用高碘酸氧化-还原胺化法对尿酸酶的N端氨基进行聚乙二醇修饰研究。首先,以相对分子质量为20 k D的单甲氧基聚乙二醇氨基盐酸盐(m PEG20000-NH2·HCl)和N-叔丁氧羰基-L-丝氨酸(Boc-Ser-OH)为原料通过酰胺化反应制备聚乙二醇中间体,然后由三氟乙酸(TFA)作用脱去Boc基团获得目标产物Ser-m PEG20000,该化合物经高碘酸钠氧化生成具有较高活性的聚乙二醇醛类衍生物,经超滤处理后即可用于蛋白质N端氨基的定点修饰,并对其修饰尿酸酶的条件进行了优化。聚乙二醇中间体和目标产物的结构通过IR和1H NMR进行表征,目标产物的总收率达72.8%。对尿酸酶的初步修饰研究表明,化合物Ser-m PEG20000具有较好的修饰蛋白的能力,对尿酸酶的最佳修饰条件为:Ser-m PEG20000与尿酸酶物质的量比为2∶1,在溶液p H 5.0条件下,于25℃反应6 h。展开更多
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.
