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    《亚洲药物制剂科学(英文版)》 2017-01
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    Mixed PEGylated surfactant modifying system decrease the accelerated blood clearance phenomenon of nanoemulsions in rats

    Yuqing Su;Wenya Tang;Yanzhi Song;Chunling Wang;Qingjing Tian;Xuling Wang;Jingjing Quan;Buoqun Li;Shaoning Wang;Yihui Deng;School of Pharmacy, Shenyang Pharmaceutical University;Beijing Sihuan-Pharm Company;School of Pharmaceutical Engineering, Shenyang Pharmaceutical University;  
    The accelerated blood clearance(ABC) phenomenon which is induced by repeated injection of poly(ethylene glycol)(PEG)-coated colloidal carriers gives clinical challenge to the promising drug delivery system. It is necessary to decrease this unexpected immunological response.A novel 4-arm poly(ethylene glycol-5000)_4-cholesteryl methyl amide(4-arm PEG_(5000)-CHMA)has been synthesized. The structure of 4-arm PEG_(5000)-CHMA was confirmed by IR and 1~H-NMR spectrum. The pharmacokinetics of the tocopheryl nicotinate(TN)-loaded nanoemulsions modified with 4-arm PEG_(5000)-CHMA or/and 1, 2-distearoyl-Sn-glycero-3-phosphoethanolamine-n-[methoxy(poly-ethyleneglycol)-2000](mPEG_(2000)-DSPE) have been studied. Furthermore, the ABC phenomenon has been detailed investigated in rats by TN-loaded nanoemulsions modified with 4-arm PEG_(5000)-CHMA and mPEG_(2000)-DSPE(CPNE). The plasma levels of TN and anti-PEG IgM antibody were determined by HPLC and ELISA, respectively.The circulation time of the CPNEs were comparable to the mPEG_(2000)-DSPE coated nanoemulsions. Moreover, the ABC phenomenon can be decreased by CPNEs. This study designs a method to decrease the ABC phenomenon and develops a clinical promising nanoemulsion for therapeutic or imaging purpose.
    【Fund】: supported by the National Natural Science Foundation of China (Grant No. 81072602 Grant No. 81373334)
    【CateGory Index】: R943
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