Dual Carfilzomib and Doxorubicin-Loaded Liposomal Nanoparticles for Synergistic Efficacy in Multiple Myeloma. 2016

Jonathan D Ashley, and Charissa J Quinlan, and Valerie A Schroeder, and Mark A Suckow, and Vincenzo J Pizzuti, and Tanyel Kiziltepe, and Basar Bilgicer
Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana.

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.

UI MeSH Term Description Entries
D008081 Liposomes Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. Niosomes,Transferosomes,Ultradeformable Liposomes,Liposomes, Ultra-deformable,Liposome,Liposome, Ultra-deformable,Liposome, Ultradeformable,Liposomes, Ultra deformable,Liposomes, Ultradeformable,Niosome,Transferosome,Ultra-deformable Liposome,Ultra-deformable Liposomes,Ultradeformable Liposome
D009101 Multiple Myeloma A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY. Myeloma, Plasma-Cell,Kahler Disease,Myeloma, Multiple,Myeloma-Multiple,Myelomatosis,Plasma Cell Myeloma,Cell Myeloma, Plasma,Cell Myelomas, Plasma,Disease, Kahler,Multiple Myelomas,Myeloma Multiple,Myeloma, Plasma Cell,Myeloma-Multiples,Myelomas, Multiple,Myelomas, Plasma Cell,Myelomas, Plasma-Cell,Myelomatoses,Plasma Cell Myelomas,Plasma-Cell Myeloma,Plasma-Cell Myelomas
D009842 Oligopeptides Peptides composed of between two and twelve amino acids. Oligopeptide
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004317 Doxorubicin Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN. Adriamycin,Adriablastin,Adriablastine,Adriblastin,Adriblastina,Adriblastine,Adrimedac,DOXO-cell,Doxolem,Doxorubicin Hexal,Doxorubicin Hydrochloride,Doxorubicin NC,Doxorubicina Ferrer Farm,Doxorubicina Funk,Doxorubicina Tedec,Doxorubicine Baxter,Doxotec,Farmiblastina,Myocet,Onkodox,Ribodoxo,Rubex,Urokit Doxo-cell,DOXO cell,Hydrochloride, Doxorubicin,Urokit Doxo cell
D004338 Drug Combinations Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. Drug Combination,Combination, Drug,Combinations, Drug
D004339 Drug Compounding The preparation, mixing, and assembly of a drug. (From Remington, The Science and Practice of Pharmacy, 19th ed, p1814). Drug Formulation,Drug Preparation,Drug Microencapsulation,Pharmaceutical Formulation,Compounding, Drug,Formulation, Drug,Formulation, Pharmaceutical,Microencapsulation, Drug,Preparation, Drug
D004353 Drug Evaluation, Preclinical Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications. Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug

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