Dual Carfilzomib and Doxorubicin-Loaded Liposomal Nanoparticles for Synergistic Efficacy in Multiple Myeloma

Here, we report the synthesis and evaluation of dual drug-loaded nanoparticles as an effective means to deliver carfilzomib and doxorubicin to multiple myeloma tumor cells at their optimal synergistic ratio. First, various molar ratios of carfilzomib to doxorubicin were screened against multiple mye...

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Bibliographic Details
Published in:Molecular cancer therapeutics 2016-07, Vol.15 (7), p.1452-1459
Main Authors: Ashley, Jonathan D, Quinlan, Charissa J, Schroeder, Valerie A, Suckow, Mark A, Pizzuti, Vincenzo J, Kiziltepe, Tanyel, Bilgicer, Basar
Format: Article
Language:English
Subjects:
Animals
Cell Line, Tumor
Disease Models, Animal
Dose-Response Relationship, Drug
Doxorubicin - administration & dosage
Doxorubicin - chemistry
Drug Combinations
Drug Compounding
Drug Evaluation, Preclinical
Drug Synergism
Humans
Liposomes - chemistry
Mice
Molecular Structure
Multiple Myeloma - drug therapy
Multiple Myeloma - pathology
Nanoparticles - chemistry
Oligopeptides - administration & dosage
Oligopeptides - chemistry
Tumor Burden - drug effects
Xenograft Model Antitumor Assays
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Summary:Here, we report the synthesis and evaluation of dual drug-loaded nanoparticles as an effective means to deliver carfilzomib and doxorubicin to multiple myeloma tumor cells at their optimal synergistic ratio. First, various molar ratios of carfilzomib to doxorubicin were screened against multiple myeloma cell lines to determine the molar ratio that elicited the greatest synergy using the Chou-Talalay method. The therapeutic agents were then incorporated into liposomes at the optimal synergistic ratio of 1:1 to yield dual drug-loaded nanoparticles with a narrow size range of 115 nm and high reproducibility. Our results demonstrated that the dual drug-loaded liposomes exhibited synergy in vitro and were more efficacious in inhibiting tumor growth in vivo than a combination of free drugs, while at the same time reducing systemic toxicity. Taken together, this study presents the synthesis and preclinical evaluation of dual drug-loaded liposomes containing carfilzomib and doxorubicin for enhanced therapeutic efficacy to improve patient outcome in multiple myeloma. Mol Cancer Ther; 15(7); 1452-9. ©2016 AACR.
ISSN:1535-7163
1538-8514
DOI:10.1158/1535-7163.MCT-15-0867