title: A noticeable phenomenon: thiol terminal PEG enhances the immunogenicity of PEGylated emulsions injected intravenously or subcutaneously into rats.
abstract: Repeated intravenous injection of long-circulating methoxy-polyethylene glycol (PEG)-liposomes alters the pharmacokinetics and biodistribution of the second administration, regarded as the "accelerated blood clearance (ABC) phenomenon." Nevertheless, the effect of terminal groups of distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG) on the induction of the ABC phenomenon had not been reported previously. In this study, rats were injected intravenously or subcutaneously with PEG coated emulsions (DE) which were prepared using PEG terminated with either the methoxyl (OCH3), hydroxyl (OH), amino (NH2), carboxyl (COOH), or thiol (SH) group. DE-OCH3 demonstrated the longest prolonged half-life in vivo after a single intravenous injection, followed by DE-SH and DE-COOH. In contrast, DE-OH was rapidly removed from the blood circulation, as was DE-NH2. Moreover, we observed a strong positive relationship between the circulation time of initially injected PEGylated emulsions and the extent to which the ABC phenomenon was induced, but a exception of DE-SH increasing the ABC effect. Furthermore, the present study suggested that thiols might stimulate the proliferation and differentiation of B cells to induce the fastest clearance of the second intravenous administration by inducing the synthesis of the cell membrane and cytosolic proteins or reacting with follicular dendritic cells. The results strongly suggested that thiol groups played a stimulatory role in the immune response and provided a considerable implication for multiple drug therapy of thiol groups.
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, PR China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Wang
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Cheng
authors.forename: Yue
authors.initials: Y
authors.lastname: Sui
authors.forename: Xiang
authors.initials: X
authors.lastname: Luo
authors.forename: Gongping
authors.initials: G
authors.lastname: Jiang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Huang
authors.forename: Zhennan
authors.initials: Z
authors.lastname: She
authors.forename: Yihui
authors.initials: Y
authors.lastname: Deng
mesh_terms: D000818:Animals; D004334:Drug Administration Schedule; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D004655:Emulsions; D006207:Half-Life; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D010714:Phosphatidylethanolamines; D013438:Sulfhydryl Compounds; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols
keywords: Accelerated blood clearance; Intravenous injection; PEGylated emulsions; Subcutaneous injection; Thiol groups