Organ distribution and tumor uptake of annamycin, a new anthracycline derivative with high affinity for lipid membranes, entrapped in multilamellar vesicles

Yiyu Zou, Waldemar Priebe, Yi He Ling, Roman Perez-Soler

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22 Citations (Scopus)

Abstract

Annamycin (Ann) is a lipophilic, non-cross resistant anthracycline antibiotic that is easily amenable to formulation in a wide variety of liposomal carriers. We studied the organ distribution and tumor uptake of Ann entrapped in multilamellar vesicles (L-Ann), free annamycin (F-Ann), and doxorubicin (DOX) in C57BL/6 mice bearing advanced subcutaneous B16 melanoma tumors. L-Ann was composed of DMPC: DMPG: Ann at a molar ratio of 7:3:0.7. Mean particle size was 1.88±0.89 μm, and the entrapment efficiency was 93.08%±2.96%. F-Ann was prepared as a suspension (particle size ≤0.2 μm) in 10% DMSO. Drug levels were measured by fluorescence spectrometry after extraction with chloroform. The extraction ratio ranged between 60% and 90% for both drugs in most tissues. Compared with those of DOX, organ AUCs of L-Ann were threefold higher in plasma and brain, twofold higher in liver and kidney, six-fold higher in lung, ninefold higher in spleen, and tenfold higher in B16 tumors. Compared with F-Ann, organ AUCs of L-Ann were twofold higher in plasma, liver, and B16 tumors and were twofold lower in brain. Heart AUCs were similar with all three drugs. Higher tumor uptake was associated with a faster penetration and more prolonged retention of Ann in tumor tissue compared with those of DOX. The results obtained indicate significant differences in organ distribution between L-Ann and DOX as a result of the higher affinity of Ann for lipid membranes and the use of the liposomes as a delivery system. The potential clinical relevance of the increased uptake of L-Ann in B16 tumors, lung, and brain is being investigated.

Original languageEnglish (US)
Pages (from-to)190-196
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume32
Issue number3
DOIs
StatePublished - May 1993
Externally publishedYes

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Anthracyclines
Membrane Lipids
Tumors
Derivatives
Neoplasms
Doxorubicin
Area Under Curve
Brain
annamycin
Particle Size
Liver
Bearings (structural)
Particle size
Pharmaceutical Preparations
Tissue
Dimyristoylphosphatidylcholine
Plasmas
Lung
Experimental Melanomas
Fluorescence Spectrometry

ASJC Scopus subject areas

  • Pharmacology
  • Oncology
  • Cancer Research

Cite this

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title = "Organ distribution and tumor uptake of annamycin, a new anthracycline derivative with high affinity for lipid membranes, entrapped in multilamellar vesicles",
abstract = "Annamycin (Ann) is a lipophilic, non-cross resistant anthracycline antibiotic that is easily amenable to formulation in a wide variety of liposomal carriers. We studied the organ distribution and tumor uptake of Ann entrapped in multilamellar vesicles (L-Ann), free annamycin (F-Ann), and doxorubicin (DOX) in C57BL/6 mice bearing advanced subcutaneous B16 melanoma tumors. L-Ann was composed of DMPC: DMPG: Ann at a molar ratio of 7:3:0.7. Mean particle size was 1.88±0.89 μm, and the entrapment efficiency was 93.08{\%}±2.96{\%}. F-Ann was prepared as a suspension (particle size ≤0.2 μm) in 10{\%} DMSO. Drug levels were measured by fluorescence spectrometry after extraction with chloroform. The extraction ratio ranged between 60{\%} and 90{\%} for both drugs in most tissues. Compared with those of DOX, organ AUCs of L-Ann were threefold higher in plasma and brain, twofold higher in liver and kidney, six-fold higher in lung, ninefold higher in spleen, and tenfold higher in B16 tumors. Compared with F-Ann, organ AUCs of L-Ann were twofold higher in plasma, liver, and B16 tumors and were twofold lower in brain. Heart AUCs were similar with all three drugs. Higher tumor uptake was associated with a faster penetration and more prolonged retention of Ann in tumor tissue compared with those of DOX. The results obtained indicate significant differences in organ distribution between L-Ann and DOX as a result of the higher affinity of Ann for lipid membranes and the use of the liposomes as a delivery system. The potential clinical relevance of the increased uptake of L-Ann in B16 tumors, lung, and brain is being investigated.",
author = "Yiyu Zou and Waldemar Priebe and Ling, {Yi He} and Roman Perez-Soler",
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AU - Zou, Yiyu

AU - Priebe, Waldemar

AU - Ling, Yi He

AU - Perez-Soler, Roman

PY - 1993/5

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AB - Annamycin (Ann) is a lipophilic, non-cross resistant anthracycline antibiotic that is easily amenable to formulation in a wide variety of liposomal carriers. We studied the organ distribution and tumor uptake of Ann entrapped in multilamellar vesicles (L-Ann), free annamycin (F-Ann), and doxorubicin (DOX) in C57BL/6 mice bearing advanced subcutaneous B16 melanoma tumors. L-Ann was composed of DMPC: DMPG: Ann at a molar ratio of 7:3:0.7. Mean particle size was 1.88±0.89 μm, and the entrapment efficiency was 93.08%±2.96%. F-Ann was prepared as a suspension (particle size ≤0.2 μm) in 10% DMSO. Drug levels were measured by fluorescence spectrometry after extraction with chloroform. The extraction ratio ranged between 60% and 90% for both drugs in most tissues. Compared with those of DOX, organ AUCs of L-Ann were threefold higher in plasma and brain, twofold higher in liver and kidney, six-fold higher in lung, ninefold higher in spleen, and tenfold higher in B16 tumors. Compared with F-Ann, organ AUCs of L-Ann were twofold higher in plasma, liver, and B16 tumors and were twofold lower in brain. Heart AUCs were similar with all three drugs. Higher tumor uptake was associated with a faster penetration and more prolonged retention of Ann in tumor tissue compared with those of DOX. The results obtained indicate significant differences in organ distribution between L-Ann and DOX as a result of the higher affinity of Ann for lipid membranes and the use of the liposomes as a delivery system. The potential clinical relevance of the increased uptake of L-Ann in B16 tumors, lung, and brain is being investigated.

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