Accelerated clearance of PEGylated liposomes in rats after repeated injections

Ishida, Tatsuhiro; Maeda, Ryuhei; Ichihara, Masako; Irimura, Kenji; Kojima, Hiroshi

doi:10.1016/s0168-3659(02)00462-5

Cited by 289 publications

(174 citation statements)

References 14 publications

Supporting

Mentioning

156

Contrasting

Unclassified

Order By: Relevance

“…24,25) on the basis of our earlier results, 26,27) we proposed the following tentative mechanism for the cause of this phenomenon: anti-PEG IgM, which is produced in the spleen in response to the first dose, selectively binds to the PEG upon the second dose of liposomes injected several days later and subsequently activates the complement system, and, as a consequence, the liposomes are taken up by Kupffer cells in the liver. A similar phenomenon was observed with polymeric micells 28,29) and PEG-modified PLA-nanoparticles.…”

Section: Anti-peg Igm Response To Pegylated Nanoparticlesmentioning

confidence: 90%

Anti-polyethyleneglycol Antibody Response to PEGylated Substances

Ishida

Kojima

2013

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

In contrast to the general assumption that polyethyleneglycol (PEG)-conjugated substances lack immunogenicity and antigenic, it has been reported that they can elicit antibodies against PEG (mainly anti-PEG immunoglobulin M (IgM)). In patients, the presence of anti-PEG antibodies may limit therapeutic efficacy of PEGylated substances as a consequence of inducing rapid clearance of and neutralizing biological activity of the substances. Here, we introduce specific examples of PEGylated substances including several PEGylated proteins and PEGylated particles (PEGylated nanocarriers) which induce anti-PEG antibody responses. Finally, we emphasize that the immunogenicity of PEGylated substances should be tested in the development stage and that the titer of anti-PEG antibodies in patients should be pre-screened and monitored prior to and throughout a course of treatment with a PEGylated substance.

show abstract

Section: Anti-peg Igm Response To Pegylated Nanoparticlesmentioning

confidence: 90%

Anti-polyethyleneglycol Antibody Response to PEGylated Substances

Ishida

Kojima

2013

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

show abstract

“…20) Briefly, the lipids were dissolved in chloroform, and after evaporation of the organic solvent, the resultant lipid film was hydrated in N-(2-hydroxyethyl) piperazine-N′2-ethanesulfonic acid (HEPES) buffered saline (25 mM HEPES, 140 mM NaCl, pH 7.4). The liposome was sized by subsequent extrusion through polycarbonate membrane filters (Nuclepore, CA, U.S.A.) with pore sizes of 400, 200, 100, and 80 nm.…”

Section: Methodsmentioning

confidence: 99%

“…10,[15][16][17][18] In contrast to the preceding argument, we and others have reported that PEGylated liposomes lose the expected long circulating property when they are injected repeatedly in the same animal (the so-called accelerated blood clearance (ABC) phenomenon). 19,20) On the basis of our earlier results, 21,22) we proposed the following tentative mechanism for the cause of this phenomenon: anti-PEG IgM, which is produced in the spleen in response to the initial dose, selectively binds to the PEG of the second dose liposomes injected several days later Regular Article * To whom correspondence should be addressed. e-mail: ishida@tokushima-u.ac.jp…”

mentioning

confidence: 98%

Intravenous Administration of Polyethylene Glycol-Coated (PEGylated) Proteins and PEGylated Adenovirus Elicits an Anti-PEG Immunoglobulin M Response

Shimizu

Ichihara

Yoshioka

et al. 2012

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

“…Examining the relationship of PL types with the ABC phenomenon is necessary to guide the correlative research if PEGylated liposomes prepared by all PL types could induce the ABC phenomenon. Previous studies usually used rats as experimental animal models, and an intense ABC phenomenon was observed (Ishida et al, 2003(Ishida et al, , 2006cKong et al, 2006;Ma et al, 2012). However, the conclusions were inconsistent with other animal models.…”

Section: Effect Of Different Pl Types On Abc Phenomenonmentioning

confidence: 99%

Influence of phospholipid types and animal models on the accelerated blood clearance phenomenon of PEGylated liposomes upon repeated injection

et al. 2014

Drug Delivery

View full text Add to dashboard Cite

(2015) Influence of phospholipid types and animal models on the accelerated blood clearance phenomenon of PEGylated liposomes upon repeated injection, Drug Delivery, 22:5, 598-607, DOI: 10.3109/10717544.2014 AbstractWhen polyethylene glycol (PEG)ylated liposomes were repeatedly injected into the same animal, the second dose of liposomes would rapidly clear from the bloodstream and enhance accumulation in the liver and spleen, and this phenomenon is called ''accelerated blood clearance (ABC)''. There are many factors known to influence ABC phenomenon, in this study, we mainly focused on the effects of different phospholipids (PL) types and animal models. The effects of PL types on ABC phenomenon were examined by repeating injection of PEGylated liposomes prepared by five different types of PL (hydrogenated soy phosphatidylcholine, egg sphingomyelin, soybean phosphatidycholin, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and egg phosphatidycholin) in rats. Dramatically, repeated injection of different types of PL could induce ABC phenomenon altogether. Both t 1/2 and AUC of experimental group (EG) were lower significantly than those of control group (CG). Our results also showed that the liver accumulation of second dose increased significantly (p50.01) in all EG as compared that of CG. Interestingly, ABC phenomenon of liposomes prepared by unsaturated PL was more obvious than that of saturated PL. All the first dose could induce the antibody (anti-PEG IgM) level increasing significantly (p50.01). For different animal models, we found that after repeated injection of PEGylated liposomes, rats, mice, rabbits and guinea pigs could produce ABC phenomenon. Various PL types and animal models could all produce the ABC phenomenon. However, their extent of accelerated clearance differed. ABC phenomenon is possibly a ubiquitous immune phenomenon in life.

show abstract

Accelerated clearance of PEGylated liposomes in rats after repeated injections

Cited by 289 publications

References 14 publications

Anti-polyethyleneglycol Antibody Response to PEGylated Substances

Anti-polyethyleneglycol Antibody Response to PEGylated Substances

Intravenous Administration of Polyethylene Glycol-Coated (PEGylated) Proteins and PEGylated Adenovirus Elicits an Anti-PEG Immunoglobulin M Response

Influence of phospholipid types and animal models on the accelerated blood clearance phenomenon of PEGylated liposomes upon repeated injection

Contact Info

Product

Resources

About