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

Asian Journal of Pharmaceutical Sciences

Wenya Tang¹  Shaoning Wang²  Yihui Deng³  Yanzhi Song³  Buoqun Li³  Qingjing Tian³  Jingjing Quan³  Yuqing Su³  Xuling Wang³  Chunling Wang³ 

[1] Beijing Sihuan-Pharm Company, China;School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016, China;School of Pharmacy, Shenyang Pharmaceutical University, 103, Wenhua Road, Shenyang 110016, China;

关键词: Accelerated blood clearance (ABC) phenomenon;    Repeated administration;    4-arm PEG5000-CHMA;    Anti-PEG IgM;   

DOI  :  10.1016/j.ajps.2016.07.003

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown