Accelerated blood clearance of PEGylated liposomes upon repeated injections: effect of doxorubicin-encapsulation and high-dose first injection.

@article{Ishida2006AcceleratedBC,
  title={Accelerated blood clearance of PEGylated liposomes upon repeated injections: effect of doxorubicin-encapsulation and high-dose first injection.},
  author={Tatsuhiro Ishida and Kazutaka Atobe and XingYu Wang and Hiroshi Kiwada},
  journal={Journal of controlled release : official journal of the Controlled Release Society},
  year={2006},
  volume={115 3},
  pages={
          251-8
        }
}
  • T. Ishida, Kazutaka Atobe, H. Kiwada
  • Published 27 October 2006
  • Biology, Chemistry
  • Journal of controlled release : official journal of the Controlled Release Society
Repeated injections of PEGylated liposomal topotecan induces accelerated blood clearance phenomenon in rats.
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It was surprising to find that repeated administration of pegylated liposomal antitumour drugs caused the disappearance of rapid distribution phase instead of the ABC phenomenon, resulting in the conversion of a two‐compartment model to a one‐compartments model.
Accelerated Blood Clearance of PEGylated PLGA Nanoparticles Following Repeated Injections: Effects of Polymer Dose, PEG Coating, and Encapsulated Anticancer Drug
TLDR
The presented results demonstrate the importance of clinical evaluations for PLGA-PEG nanocarriers that consider the administration schedule in multiple drug delivery, particularly in cancer chemotherapy.
Accelerated blood clearance of pegylated liposomal topotecan: influence of polyethylene glycol grafting density and animal species.
TLDR
It was found that repeated injection of pegylated liposomal topotecan could induce ABC phenomenon in Wistar rats, beagle dogs, and mice, which might be associated with the formation of empty liposomes in circulation because of the rapid drug release rate.
Accelerated drug release and clearance of PEGylated epirubicin liposomes following repeated injections: a new challenge for sequential low-dose chemotherapy
TLDR
It is implied that the accelerated blood clearance phenomenon and its accompanying rapid leakage and clearance of drug following sequential low-dose injections may reverse the unique pharmacokinetic–toxicity profile of liposomes.
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References

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Factors affecting the accelerated blood clearance of polyethylene glycol-liposomes upon repeated injection.
TLDR
The results indicate that hepatosplenic macrophages play an essential role in the enhanced clearance effect and that the change in pharmacokinetic behavior upon repeated injection is a general characteristic of liposomes, unrelated to the presence of PEG.
Accelerated clearance of PEGylated liposomes in rats after repeated injections.
Injection of PEGylated liposomes in rats elicits PEG-specific IgM, which is responsible for rapid elimination of a second dose of PEGylated liposomes.
  • T. Ishida, M. Ichihara, H. Kiwada
  • Biology, Chemistry
    Journal of controlled release : official journal of the Controlled Release Society
  • 2006
Immunogenicity and Rapid Blood Clearance of Liposomes Containing Polyethylene Glycol-Lipid Conjugates and Nucleic Acid
TLDR
It is reported that liposome compositions containing PEG-lipid derivatives and encapsulated antisense oligodeoxynucleotide (ODN) or plasmid DNA elicit a strong immune response that results in the rapid blood clearance of subsequent doses in mice, sufficient to induce significant morbidity and, in some instances, mortality.
Accelerated blood clearance and altered biodistribution of repeated injections of sterically stabilized liposomes.
TLDR
Administration of sterically stabilized PEG liposomes significantly altered the pharmacokinetic behavior of subsequently injected PEGliposomes in a time- and frequency-dependent manner, and the observed phenomenon may have important implications for the repeated administration of sterially stabilized liposome for targeted drug delivery.
Spleen plays an important role in the induction of accelerated blood clearance of PEGylated liposomes.
Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes.
TLDR
The results of this study are consistent with preclinical findings indicating that the pharmacokinetics of doxorubicin are drastically altered using Doxil and follow a pattern dictated by the liposome carrier.
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