• Corpus ID: 14452614

Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes.

@article{Gabizon1994ProlongedCT,
  title={Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes.},
  author={Alberto A. Gabizon and Raphael Catane and Beatrice Uziely and Bella Kaufman and Tamar Safra and Rivka Cohen and Francis J. Martin and Anthony Huang and Yechezkel Barenholz},
  journal={Cancer research},
  year={1994},
  volume={54 4},
  pages={
          987-92
        }
}
In preclinical studies, a doxorubicin liposome formulation containing polyethylene-glycol (Doxil) shows a long circulation time in plasma, enhanced accumulation in murine tumors, and a superior therapeutic activity over free (unencapsulated) doxorubicin (DOX. [] Key Method The pharmacokinetics of doxorubicin and/or liposome-associated doxorubicin were analyzed in seven patients after injections of equivalent doses of free DOX and Doxil and in an additional group of nine patients after injection of Doxil…

Figures and Tables from this paper

Clinical studies of liposome-encapsulated doxorubicin.

TLDR
Polyethyleneglycol-coated liposomes show a distinct advantage over previous liposome formulations directed at the RES and appear to be a promising drug delivery system for doxorubicin.

Pegylated liposomal doxorubicin: proof of principle using preclinical animal models and pharmacokinetic studies.

TLDR
Encapsulation of doxorubicin in polyethylene glycol-coated liposomes (Doxil/Caelyx [PLD], was developed to enhance the safety and efficacy of conventional doxorbicin and has potential applications to treat a variety of cancers.

Comparative study of the antitumor activity of free doxorubicin and polyethylene glycol-coated liposomal doxorubicin in a mouse lymphoma model.

TLDR
Overall, Doxil given by the systemic i.v. route was the most effective treatment in prolonging median survival and obtaining cures and variations in the dose-schedule treatment regime confirm the superior therapeutic profile and reduced dependence on tumor burden of the PEGylated liposomal formulation over free drug.

Pegylated Liposomal Doxorubicin: Metamorphosis of an Old Drug into a New Form of Chemotherapy

  • A. Gabizon
  • Biology, Medicine
    Cancer investigation
  • 2001
TLDR
Doxil toxicity profile is drastically different from that of doxorubicin, and is characterized by dominant and dose-limiting mucocutaneous toxicities, mild myelosupression, minimal alopecia, and no apparent cardiac toxicity.

Clinical pharmacology of liposomal anthracyclines: focus on pegylated liposomal Doxorubicin.

TLDR
Pegylated liposomal doxorubicin has been approved for clinical use in a variety of neoplastic conditions because of its antitumor efficacy and unique safety profile with an impressive reduction of cardiac toxicity in comparison with conventional doxorbicin.

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.

Development of liposomal anthracyclines: from basics to clinical applications.

Improved pharmacokinetics and reduced side effects of doxorubicin therapy by liposomal co-encapsulation with curcumin

TLDR
It is demonstrated that the liposomal association of CURC and DOX effectively improved the pharmacokinetics and biodistribution of DOX, limiting its side effects, via C URC-dependent antioxidant effects.

Pharmacokinetic and cytotoxic studies of pegylated liposomal daunorubicin

TLDR
Results revealed that liposomal daunorubicin significantly reduced the toxicity of the drug, with a half lethal dose, compared with 5.45 mg/kg for free drug, and pegylated liposome-loaded DNR may be a promising anticancer drug and worth further therapeutic study.
...

References

SHOWING 1-10 OF 35 REFERENCES

Pharmacokinetics and tissue distribution of doxorubicin encapsulated in stable liposomes with long circulation times.

TLDR
Both types of liposomes reduced considerably the amount of drug accumulating in the heart compared with that accumulating after injection of free DXR, and peak drug concentrations in the liver were observed in agreement with the plasma clearance curves.

Selective tumor localization and improved therapeutic index of anthracyclines encapsulated in long-circulating liposomes.

TLDR
Evidence is provided that anthracyclines delivered in long-circulating liposomes extravasate with relative selectivity in tumor areas, improving the overall therapeutic index is provided, as well as reducing the lethal toxicity of the drug in mice.

Systemic administration of doxorubicin-containing liposomes in cancer patients: a phase I study.

Pharmacokinetic and imaging studies in patients receiving a formulation of liposome-associated adriamycin.

TLDR
Plasma clearance of total drug extracted from the plasma after L-ADM infusion followed a biexponential curve with a pattern similar to that reported for free ADM, and liposome-associated drug was found to be rapidly cleared from plasma.

Antitumor activity of liposome-encapsulated doxorubicin in advanced breast cancer: phase II study.

TLDR
LED was used to treat 20 patients with advanced, measurable breast cancer and alopecia occurred in all patients and usually was complete, while Gastrointestinal toxicity and mucositis were generally mild and tolerable.

Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors.

TLDR
By selective changes in lipid composition, up to a 60-fold increase in the fraction of recovered dose present in blood 24 hr after i.v. injection is achieved, which has considerable therapeutic potential in cancer for increasing the concentration of cytotoxic agents in tumors while minimizing the likelihood of toxicity to the reticuloendothelial system.

Preclinical and Clinical Experience with a Doxorubicin-Liposome Preparation

TLDR
Preclinical and phase I clinical data with liposome-associated doxorubicin are reviewed and it is suggested that the maximal tolerated dosage is significantly increased over that of the free drug and that the reticuloendothelial system is responsible for the rapid and dominant pathway of liposomes clearance.

Therapy of primary and metastatic mouse mammary carcinomas with doxorubicin encapsulated in long circulating liposomes

TLDR
The Stealth liposome formulation was significantly more effective than the conventional liposomes formulation or the free drug in reducing the incidence of metastases from intra‐mammary implants of tumor MC19 and tumor MC65, in curing mice with recent implants of tumors MC2A, tumor MC2B, and tumorMC65, and in increasing the 8‐week survival of mice with well‐established implants ofcancer.

A phase I clinical trial and pharmacokinetic evaluation of liposome-encapsulated doxorubicin.

  • A. RahmanJ. Treat P. Woolley
  • Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 1990
TLDR
LED was well tolerated and produced only moderate nausea and vomiting and little stomatitis at myelosuppressive doses, and it is suggested that LED produces less venous sclerosis than free doxorubicin, but this requires further clinical verification.

Effect of liposome composition and other factors on the targeting of liposomes to experimental tumors: biodistribution and imaging studies.

TLDR
The contention that some glycolipid-containing liposomes previously shown to have long circulating half-lives accumulate significantly in a variety of tumors and are promising tools for the delivery of anti-tumor agents is supported.