title: Accelerated blood clearance phenomenon upon cross-administration of PEGylated nanocarriers in beagle dogs.
abstract: The cross-administration of nanocarriers modified by poly(ethylene glycol) (PEG), named PEGylated nanocarriers, a type of combination therapy, is becoming an increasingly important method of long-term drug delivery, to decrease side effects, avoid multidrug resistance, and increase therapeutic efficacy. However, repeated injections of PEGylated nanocarriers induces the accelerated blood clearance (ABC) phenomenon, prevents long circulation, and can cause adverse effects owing to alterations in the biodistribution of the drug. Although the nature of the ABC phenomenon that is induced by repeated injections of PEGylated nanocarriers has already been studied in detail, there are few reports on the immune response elicited by the cross-administration of PEGylated nanocarriers. In this study, we investigated the ABC phenomenon induced by the intravenous cross-administration of various PEGylated nanocarriers, including PEGylated liposomes (PL), PEG micelles (PM), PEGylated solid lipid nanoparticles (PSLN), and PEGylated emulsions (PE), in beagle dogs. The results indicated that the magnitude of the immune response elicited by the cross-administration was in the following order (from the strongest to the weakest): PL, PE, PSLN, PM. It is specifically PEG in the brush structure that elicits a significant immune response, in both the induction phase and the effectuation phase. Furthermore, the present study suggests that there is a considerable difference between the effect of repeated injections and cross-administration, depending on the colloidal structure. This work is a preliminary investigation into the cross-administration of PEGylated nanocarriers, and our observations can have serious implications for the design of combination therapies that use PEGylated vectors.
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Wang
authors.affiliation: Deli Wei Biological Technology Co, Ltd, Beijing, People's Republic of China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Cheng
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Su
authors.affiliation: Shenyang Women's and Children's Hospital, Shenyang, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Pei
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Yanzhi
authors.initials: Y
authors.lastname: Song
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Jiao
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Huang
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Ma
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Yinming
authors.initials: Y
authors.lastname: Dong
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yao
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Fan
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Han
authors.initials: H
authors.lastname: Ta
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Yihui
authors.initials: Y
authors.lastname: Deng
mesh_terms: D000818:Animals; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D004655:Emulsions; D008081:Liposomes; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D008081:Liposomes; D008823:Micelles; D011092:Polyethylene Glycols
keywords: ABC phenomenon; PEGylated nanocarriers; cross-administration; immune response; repeated injection