Size-dependent induction of accelerated blood clearance phenomenon by repeated injections of polymeric micelles

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• 作者：Hiroyuki Koide^a ; ^b ; Tomohiro Asai^a ; Hiroki Kato^a ; Hidenori Ando^a ; Kouichi Shiraishi^c ; Masayuki Yokoyama^c ; Naoto Oku^a ; ^{oku@u-shizuoka-ken.ac.jp}
• 关键词：ABC phenomenon ; accelerated blood clearance phenomenon ; MPEG-DSPE ; 1 ; 2-distearoyl-sn-glycero-3-phosphoethanolamine-n-[methoxy(polyethylene glycol)-2000] ; PM-30 ; polymeric micelles composed of PEG-poly[Asp(pentyl)] ; PM-75 ; polymeric micelles composed of PE
• 刊名：International Journal of Pharmaceutics
• 出版年：2012
• 期刊代码：24_03785173
• 类别：pha
• 出版时间：1 August, 2012
• 卷：432
• 期：1-2
• 页码：75-79
• 文件大小：521 K

摘要

An accelerated blood clearance (ABC) phenomenon is induced by repeated injections of poly(ethylene glycol)-modified (PEGylated) liposomes. We previously indicated that the phenomenon was induced by polymeric micelles possessing PEG chains like as liposomes, although, the induction mechanism of the ABC phenomenon is not fully elucidated. In the present study, we investigate whether repeat-injection of the polymeric micelles having PEG chains trigger the phenomenon or not. Two polymeric micelles, PM-30 (polymeric micelles with 33.6 nm in diameter) and PM-75 (76.2 nm), were prepared with PEG-poly[Asp(pentyl)] and PEG-poly[Asp(nonyl)], respectively. We firstly examined the ABC-triggering effect of these micelles, and observed that both polymeric micelles, especially PM-75, induced the production of anti-PEG IgM antibody in treated mice. Then, PM-30 or PM-75 was preadministered into mice as a preconditioning. Seven days later, AlexaFluor594-labeled PM-30 or PM-75 was administered to determine the susceptibility of the phenomenon. As a result, rapid clearance of AlexaFluor594-labeled PM-75 from the bloodstream and accumulation in the liver were observed in PM-75 pretreated mice. Although, the ABC phenomenon of AlexaFluor594-labeled PM-30 was less obvious in PM-30 pretreated mice. Our present results indicated that the repeated injections of polymeric micelles caused the ABC phenomenon in a size-dependent manner.