Effect of vesicle size and lipid composition on the in vivo tumor selectivity and toxicity of the non-cross-resistant anthracycline annamycin incorporated in liposomes

Yiyu Zou, Y. H. Lin, S. Reddy, W. Priebe, Roman Perez-Soler

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Annamycin (Ann) is a non-cross-resistant lipophilic anthracycline antibiotic optimally suited for liposome delivery. We studied how vesicle size and presence of phospholipids with a high phase transition temperature and monosialoganglioside (GM1) in the liposome bilayers affect the pharmacokinetics, tumor selectivity and toxicity of Ann. Entrapment of Ann in multilamellar vesicles (L-Ann) resulted in a 20% lower heart AUC and a 30-40% higher tumor and liver AUC. Reduction of the liposome size from 1.6 to 0.03 μm increased Ann plasma circulation time and tumor AUC by 2-fold, enhanced Ann tumor selectivity and decreased Ann subacute toxicity by 2-fold. The presence of phospholipids with a high phase transition temperature and GM1 in the liposome bilayers further prolonged Ann plasma circulation time by 2- to 4-fold, did not increase Ann tumor AUC and moderately increased Ann subacute toxicity. The anti-tumor activity of Ann correlated with the tumor AUC achieved with each particular formulation. Our results strongly suggest that vesicle size may be an important determinant of the therapeutic index of liposomal Ann, but they fail to demonstrate a beneficial tumor-targeting effect of liposomes composed of GM1 and phospholipids with a high phase transition temperature, as has been reported for the hydrophilic parent compound doxorubicin.

Original languageEnglish (US)
Pages (from-to)666-671
Number of pages6
JournalInternational Journal of Cancer
Volume61
Issue number5
DOIs
StatePublished - 1995
Externally publishedYes

Fingerprint

Anthracyclines
Liposomes
Lipids
Neoplasms
Area Under Curve
Transition Temperature
Phase Transition
Phospholipids
annamycin
Doxorubicin
Pharmacokinetics
Anti-Bacterial Agents

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{19b115179d70464286bacae8ae74d6f4,
title = "Effect of vesicle size and lipid composition on the in vivo tumor selectivity and toxicity of the non-cross-resistant anthracycline annamycin incorporated in liposomes",
abstract = "Annamycin (Ann) is a non-cross-resistant lipophilic anthracycline antibiotic optimally suited for liposome delivery. We studied how vesicle size and presence of phospholipids with a high phase transition temperature and monosialoganglioside (GM1) in the liposome bilayers affect the pharmacokinetics, tumor selectivity and toxicity of Ann. Entrapment of Ann in multilamellar vesicles (L-Ann) resulted in a 20{\%} lower heart AUC and a 30-40{\%} higher tumor and liver AUC. Reduction of the liposome size from 1.6 to 0.03 μm increased Ann plasma circulation time and tumor AUC by 2-fold, enhanced Ann tumor selectivity and decreased Ann subacute toxicity by 2-fold. The presence of phospholipids with a high phase transition temperature and GM1 in the liposome bilayers further prolonged Ann plasma circulation time by 2- to 4-fold, did not increase Ann tumor AUC and moderately increased Ann subacute toxicity. The anti-tumor activity of Ann correlated with the tumor AUC achieved with each particular formulation. Our results strongly suggest that vesicle size may be an important determinant of the therapeutic index of liposomal Ann, but they fail to demonstrate a beneficial tumor-targeting effect of liposomes composed of GM1 and phospholipids with a high phase transition temperature, as has been reported for the hydrophilic parent compound doxorubicin.",
author = "Yiyu Zou and Lin, {Y. H.} and S. Reddy and W. Priebe and Roman Perez-Soler",
year = "1995",
doi = "10.1002/ijc.2910610513",
language = "English (US)",
volume = "61",
pages = "666--671",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "5",

}

TY - JOUR

T1 - Effect of vesicle size and lipid composition on the in vivo tumor selectivity and toxicity of the non-cross-resistant anthracycline annamycin incorporated in liposomes

AU - Zou, Yiyu

AU - Lin, Y. H.

AU - Reddy, S.

AU - Priebe, W.

AU - Perez-Soler, Roman

PY - 1995

Y1 - 1995

N2 - Annamycin (Ann) is a non-cross-resistant lipophilic anthracycline antibiotic optimally suited for liposome delivery. We studied how vesicle size and presence of phospholipids with a high phase transition temperature and monosialoganglioside (GM1) in the liposome bilayers affect the pharmacokinetics, tumor selectivity and toxicity of Ann. Entrapment of Ann in multilamellar vesicles (L-Ann) resulted in a 20% lower heart AUC and a 30-40% higher tumor and liver AUC. Reduction of the liposome size from 1.6 to 0.03 μm increased Ann plasma circulation time and tumor AUC by 2-fold, enhanced Ann tumor selectivity and decreased Ann subacute toxicity by 2-fold. The presence of phospholipids with a high phase transition temperature and GM1 in the liposome bilayers further prolonged Ann plasma circulation time by 2- to 4-fold, did not increase Ann tumor AUC and moderately increased Ann subacute toxicity. The anti-tumor activity of Ann correlated with the tumor AUC achieved with each particular formulation. Our results strongly suggest that vesicle size may be an important determinant of the therapeutic index of liposomal Ann, but they fail to demonstrate a beneficial tumor-targeting effect of liposomes composed of GM1 and phospholipids with a high phase transition temperature, as has been reported for the hydrophilic parent compound doxorubicin.

AB - Annamycin (Ann) is a non-cross-resistant lipophilic anthracycline antibiotic optimally suited for liposome delivery. We studied how vesicle size and presence of phospholipids with a high phase transition temperature and monosialoganglioside (GM1) in the liposome bilayers affect the pharmacokinetics, tumor selectivity and toxicity of Ann. Entrapment of Ann in multilamellar vesicles (L-Ann) resulted in a 20% lower heart AUC and a 30-40% higher tumor and liver AUC. Reduction of the liposome size from 1.6 to 0.03 μm increased Ann plasma circulation time and tumor AUC by 2-fold, enhanced Ann tumor selectivity and decreased Ann subacute toxicity by 2-fold. The presence of phospholipids with a high phase transition temperature and GM1 in the liposome bilayers further prolonged Ann plasma circulation time by 2- to 4-fold, did not increase Ann tumor AUC and moderately increased Ann subacute toxicity. The anti-tumor activity of Ann correlated with the tumor AUC achieved with each particular formulation. Our results strongly suggest that vesicle size may be an important determinant of the therapeutic index of liposomal Ann, but they fail to demonstrate a beneficial tumor-targeting effect of liposomes composed of GM1 and phospholipids with a high phase transition temperature, as has been reported for the hydrophilic parent compound doxorubicin.

UR - http://www.scopus.com/inward/record.url?scp=0029006392&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029006392&partnerID=8YFLogxK

U2 - 10.1002/ijc.2910610513

DO - 10.1002/ijc.2910610513

M3 - Article

C2 - 7768640

AN - SCOPUS:0029006392

VL - 61

SP - 666

EP - 671

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 5

ER -