Novel Amiodarone−Doxorubicin Cocktail Liposomes Enhance Doxorubicin Retention and Cytotoxicity in DU145 Human Prostate Carcinoma Cells

We have developed novel cocktail liposomes bearing doxorubicin in their hydrophilic cores, and amiodarone, a potent multidrug resistance inhibitor, in their lipid bilayers. The efficacy of these liposomes was studied in DU145 human prostate carcinoma cells. Intracellular calcein retention, which is...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2008-10, Vol.51 (19), p.6067-6074
Main Authors: Theodossiou, Theodossis A, Galanou, Maria C, Paleos, Constantinos M
Format: Article
Language:English
Subjects:
Amiodarone - chemical synthesis
Amiodarone - chemistry
Amiodarone - pharmacology
Antineoplastic agents
Biological and medical sciences
Cell Proliferation - drug effects
Dose-Response Relationship, Drug
Doxorubicin - chemical synthesis
Doxorubicin - chemistry
Doxorubicin - pharmacology
Drug Resistance, Multiple - drug effects
Drug Resistance, Neoplasm - drug effects
Drug Screening Assays, Antitumor
Fluorescence
General aspects
Humans
Lipid Bilayers - chemistry
Liposomes
Male
Medical sciences
Microscopy, Confocal
Molecular Structure
Pharmacology. Drug treatments
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Structure-Activity Relationship
Time Factors
Tumor Cells, Cultured
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Summary:We have developed novel cocktail liposomes bearing doxorubicin in their hydrophilic cores, and amiodarone, a potent multidrug resistance inhibitor, in their lipid bilayers. The efficacy of these liposomes was studied in DU145 human prostate carcinoma cells. Intracellular calcein retention, which is inversely proportional to multidrug resistance activity, significantly increased following cell incubation with amiodarone loaded liposomes. Fluorescence confocal microscopy on cells incubated with the cocktail liposomes revealed enhanced intranuclear doxorubicin accumulation. Two liposomal drug concentration combinations were employed to assess the differential cytotoxicity of the cocktail liposomes, doxorubicin (1.4 μM)−amiodarone (15 μM) and doxorubicin 3 (μM)−amiodarone (45 μM), and two incubation times, 5 and 19 h. Cell toxicity was determined by XTT assays at 24, 48, and 72 h following incubation and was significantly enhanced for incubation with the cocktail liposomes. On the whole, we believe that these liposomes will greatly contribute to the cancer chemotherapy arena.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm800493j