Mixed PEGylated surfactant modifying system decrease the accelerated blood clearance phenomenon of nanoemulsions in rats

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• 作者：Yuqing Su^a ; Wenya Tang^b ; Yanzhi Song^a ; Chunling Wang^a ; Qingjing Tian^a ; Xuling Wang^a ; Jingjing Quan^a ; Buoqun Li^a ; Shaoning Wang^c ; ^{wsn-xh@126.com} ; Yihui Deng^a ; ^{pharmdeng@gmail.com}
• 关键词：Accelerated blood clearance (ABC) phenomenon ; Repeated administration ; 4-arm PEG5000-CHMA ; Anti-PEG IgM
• 刊名：Asian Journal of Pharmaceutical Sciences
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：12
• 期：1
• 页码：28-36
• 全文大小：1575 K
• 卷排序：12

文摘

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 PEG5000-CHMA) has been synthesized. The structure of 4-arm PEG5000-CHMA was confirmed by IR and 1H-NMR spectrum. The pharmacokinetics of the tocopheryl nicotinate (TN)-loaded nanoemulsions modified with 4-arm PEG5000-CHMA or/and 1, 2-distearoyl-Sn-glycero-3-phosphoethanolamine-n-[methoxy(poly-ethyleneglycol)-2000] (mPEG2000-DSPE) have been studied. Furthermore, the ABC phenomenon has been detailed investigated in rats by TN-loaded nanoemulsions modified with 4-arm PEG5000-CHMA and mPEG2000-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 mPEG2000-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.