Novel amiodarone-doxorubicin cocktail liposomes enhance doxorubicin retention and cytotoxicity in DU145 human prostate carcinoma cells.

Abstract

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 microM)-amiodarone (15 microM) and doxorubicin 3 (microM)-amiodarone (45 microM), 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.

• Authors: Theodossis A Theodossiou, Maria C Galanou, Constantinos M Paleos
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 51 Issue 19 Pg. 6067-74 (Oct 09 2008) ISSN: 1520-4804 [Electronic] United States
• PMID: 18783209 (Publication Type: Journal Article)

Chemical References

• Lipid Bilayers
• Liposomes
• Doxorubicin
• Amiodarone

Topics

• Amiodarone (chemical synthesis, chemistry, pharmacology)
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Doxorubicin (chemical synthesis, chemistry, pharmacology)
• Drug Resistance, Multiple (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Drug Screening Assays, Antitumor
• Fluorescence
• Humans
• Lipid Bilayers (chemistry)
• Liposomes
• Male
• Microscopy, Confocal
• Molecular Structure
• Prostatic Neoplasms (drug therapy, metabolism, pathology)
• Structure-Activity Relationship
• Time Factors
• Tumor Cells, Cultured