title: [Elucidation of accelerated blood clearance phenomenon caused by repeat injection of PEGylated nanocarriers].
abstract: Liposomes modified with polyethylene glycol (PEG) can stably exist in the bloodstream because the PEG on the liposomes attracts a water shell to the liposomal surface. Since these liposomes are long circulating nanocarriers, they are used as drug and gene delivery tools. Repeat injection of PEGylated liposomes, however, is known to induce the accelerated blood clearance (ABC) phenomenon. In the ABC phenomenon, PEGylated liposomes that are injected subsequent to the first injection are cleared rapidly from the bloodstream and accumulate in the liver, resulting in loss of their long-circulating characteristics. The induction of ABC phenomenon is related to the production of anti-PEG IgM from splenic B cells. To elucidate the mechanism of the phenomenon, we firstly examined the relationship between the induction of ABC phenomenon and the concentration of PEGylated liposomes, and observed that the high dose of those did not induce the phenomenon. Next, we investigated whether polymeric micelles trigger ABC phenomenon or not. Finally, the size-dependency of ABC phenomenon was investigated by use of variously sized PEGylated liposomes and polymeric micelles having PEG chains. Our data suggest that the initiation of ABC phenomenon would be size-dependent, and particles smaller than 30 nm did not induce ABC phenomenon. We anticipate that the elucidation of the ABC phenomenon will be helpful for the development of DDS formulations.
authors: Department of Medical Biochemistry, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors: Hiroyuki
authors: H
authors: Koide
authors: Tomohiro
authors: T
authors: Asai
authors: Kentaro
authors: K
authors: Hatanaka
authors: Kosuke
authors: K
authors: Shimizu
authors: Masayuki
authors: M
authors: Yokoyama
authors: Tatsuhiro
authors: T
authors: Ishida
authors: Hiroshi
authors: H
authors: Kiwada
authors: Naoto
authors: N
authors: Oku
mesh_terms: D004337:Drug Carriers; D016503:Drug Delivery Systems; D055808:Drug Discovery; D018014:Gene Transfer Techniques; D008081:Liposomes; D008657:Metabolic Clearance Rate; D008823:Micelles; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D011092:Polyethylene Glycols
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D008823:Micelles; D011092:Polyethylene Glycols