Injection of PEGylated liposomes in rats elicits PEG-specific IgM, which is responsible for rapid elimination of a second dose of PEGylated liposomes

Ishida, Tatsuhiro; Ichihara, Masako; Wang, Xinyu; Yamamoto, Kiyomi; Kimura, Junji; Majima, Eiji; Kojima, Hiroshi

doi:10.1016/j.jconrel.2006.01.005

Cited by 483 publications

(373 citation statements)

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“…CH 50 was determined according to the method described previously 22) with sheep red blood cells sensitized with monoclonal anti-sheep IgM antibody (SRBC) (CH 50 SEIKEN, DENKA SEIKEN, Tokyo, Japan). Briefly, 90 µL of rat serum was collected from rats that had received an intravenous injection of PEG-BSAs (1 µg protein/animal), PEGylated liposome (0.0002 µmol phospholipids/animal) or HEPES.…”

Section: Preparation Of Pegylated Adenoviruses (Ads)mentioning

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…”

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confidence: 98%

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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

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Section: Preparation Of Pegylated Adenoviruses (Ads)mentioning

confidence: 99%

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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

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“…Also, it is important to note that no adverse reactions were observed in the animals from the final 3-mg/kg dose when antibodies were present. This result contrasts with the adverse reactions observed with repeated administration of lipid-based systems that are associated with the presence of antibodies (22,23,(25)(26)(27)(28).…”

Section: Multiple Doses Of Targeted Nanoparticles Safely Administered Inmentioning

confidence: 60%

Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNA

Heidel

Liu

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

357

227

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The results of administering escalating, i.v. doses of targeted nanoparticles containing a siRNA targeting the M2 subunit of ribonucleotide reductase to non-human primates are reported. The nanoparticles consist of a synthetic delivery system that uses a linear, cyclodextrin-containing polycation, transferrin (Tf) protein targeting ligand, and siRNA. When administered to cynomolgus monkeys at doses of 3 and 9 mg siRNA/kg, the nanoparticles are well tolerated. At 27 mg siRNA/kg, elevated levels of blood urea nitrogen and creatinine are observed that are indicative of kidney toxicity. Mild elevations in alanine amino transferase and aspartate transaminase at this dose level indicate that the liver is also affected to some extent. Analysis of complement factors does not reveal any changes that are clearly attributable to dosing with the nanoparticle formulation. Detection of increased IL-6 levels in all animals at 27 mg siRNA/kg and increased IFN-␥ in one animal indicate that this high dose level produces a mild immune response. Overall, no clinical signs of toxicity clearly attributable to treatment are observed. The multiple administrations spanning a period of 17-18 days enable assessment of antibody formation against the human Tf component of the formulation. Low titers of anti-Tf antibodies are detected, but this response is not associated with any manifestations of a hypersensitivity reaction upon readministration of the targeted nanoparticle. Taken together, the data presented show that multiple, systemic doses of targeted nanoparticles containing nonchemically modified siRNA can safely be administered to non-human primates.systemic administration ͉ RNA interference

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“…Ishida et al [44] demonstrated that the elimination t 1/2 of the second dose of PEGylated liposomes injected within 2 days after the first dose was the same as the control ( ∼ 15 h). The ABC phenomenon started to occur in 3 days (t 1/2 = 6 h), maximized in 4 -5 days (t 1/2 = 0.3 -0.5 h) and persisted for at least 2 weeks, but the effect was gradually diminished after 5 days post the first injection.…”

Section: Interval Between Injectionsmentioning

confidence: 96%

Immune responses of therapeutic lipid nanoparticles

Chen¹,

May²,

Li³

2013

Nanotechnology Reviews

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Nanoparticle-based drug delivery is an emerging technology for targeting therapeutics to the diseased site for enhanced therapy and reduced toxicity. A number of pharmaceutical products that involve nanotechnology have been approved for clinical use, and because of altered pharmacokinetics and biodistribution, their profiles of interaction with host cells and resulting toxicity are different from parent agents. This review focuses on the immune responses induced by therapeutic lipid nanoparticles. These immune responses can provoke toxicity, affect pharmacokinetics of the nanoparticles or induce therapeutic effect. This article begins with a general introduction on immune responses and innate and acquired immunity. Specific examples of therapeutic lipid nanoparticles inducing immune responses in each category are presented with detailed discussions on the mechanisms. Current guidelines for evaluating immune response of nanomedicines are summarized. Finally, perspectives and future directions are provided emphasizing mechanistic studies of immune reactions triggered by nanoparticles.

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Injection of PEGylated liposomes in rats elicits PEG-specific IgM, which is responsible for rapid elimination of a second dose of PEGylated liposomes

Cited by 483 publications

References 34 publications

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

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

Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNA

Immune responses of therapeutic lipid nanoparticles

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