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

• Published in: Asian journal of pharmceutical sciences 2017-01, Vol.12 (1), p.28-36
• Main Authors: Su, Yuqing, Tang, Wenya, Song, Yanzhi, Wang, Chunling, Tian, Qingjing, Wang, Xuling, Quan, Jingjing, Li, Buoqun, Wang, Shaoning, Deng, Yihui
• Format: Article
• Language: English
• Subjects: 4-arm PEG5000-CHMA; Accelerated blood clearance (ABC) phenomenon; Anti-PEG IgM; Original; Repeated administration
• ISSN: 1818-0876; 2221-285X
• DOI: 10.1016/j.ajps.2016.07.003

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.