Pharmacokinetics of Pegylated Liposomal Doxorubicin

@article{Gabizon2003PharmacokineticsOP,
  title={Pharmacokinetics of Pegylated Liposomal Doxorubicin},
  author={Alberto A. Gabizon and Hilary Shmeeda and Yechezkel Barenholz},
  journal={Clinical Pharmacokinetics},
  year={2003},
  volume={42},
  pages={419-436}
}
Pegylated liposomal doxorubicin (doxorubicin HCl liposome injection; Doxil® or Caelyx®) is a liposomal formulation of doxorubicin, reducing uptake by the reticulo-endothelial system due to the attachment of polyethylene glycol polymers to a lipid anchor and stably retaining drug as a result of liposomal entrapment via an ammonium sulfate chemical gradient. These features result in a pharmacokinetic profile characterised by an extended circulation time and a reduced volume of distribution… 
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TLDR
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TLDR
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References

SHOWING 1-10 OF 74 REFERENCES
Development of liposomal anthracyclines: from basics to clinical applications.
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.
Dose Dependency of Pharmacokinetics and Therapeutic Efficacy of Pegylated Liposomal Doxorubicin (DOXIL) in Murine Models
TLDR
D dose escalation results in a saturation of Doxil clearance and a disproportional increase of the amount of liposomal drug accumulating in tumor, and a trend to superior therapeutic efficacy for treatments based on larger doses as compared to smaller split doses, while maintaining an equivalent dose intensity was observed.
Pharmacokinetics, Biodistribution and Therapeutic Efficacy of Doxorubicin Encapsulated in Stealth® Liposomes (Doxil®)
TLDR
Doxil exhibits altered plasma pharmacokinetics, with a longer plasma half-life, large AUC and markedly smaller volume of distribution than Adriamycin and Tissue levels of doxorubicin are generally lo...
Preclinical Studies with Doxorubicin Encapsulated in Polyethyleneglycol-Coated Liposomes
TLDR
The minimal lethal dose of DOX to tumor-free mice was substantially increased by encapsulation in PEG-coated liposomes, indicating that toxicity is reduced and the vesicant ofDOX after intradermal injection is prevented by liposome encapsulation.
Direct comparison of liposomal doxorubicin with or without polyethylene glycol coating in C-26 tumor-bearing mice: is surface coating with polyethylene glycol beneficial?
  • R. Hong, C. Huang, F. Chang
  • Chemistry, Biology
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 1999
TLDR
Although both liposomal groups were better than the free drug group in terms of clinically relevant parameters, including toxicity, tumor shrinkage, and survival, there was no difference between the twoliposomal drug groups.
Sterically stabilized liposomes.
Tumour uptake of doxorubicin in polyethylene glycol-coated liposomes and therapeutic effect against a xenografted human pancreatic carcinoma.
TLDR
This study tested the therapeutic efficacy of doxorubicin hydrochloride in two formulations: free in saline suspension and encapsulated in polyethylene glycol-coated, long-circulating liposomes, finding liposome-encapsulation was significantly more effective in inhibiting tumour growth and in effecting cures.
Doxorubicin encapsulated in sterically stabilized liposomes for the treatment of a brain tumor model: biodistribution and therapeutic efficacy.
TLDR
The authors conclude that the use of long-circulating liposomes as cytotoxic drug carriers in brain tumor results in enhanced drug exposure and improved therapeutic activity, with equal effectiveness against early small- and large-sized brain tumors.
...
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