Biophysical characterization of a liposomal formulation of cytarabine and daunorubicin
Abstract
The biophysical characterization of CPX-351, a liposomal formulation of cytarabine and daunorubicin encapsulated in a synergistic 5:1 molar ratio (respectively), is presented. CPX-351 is a promising drug candidate currently in two concurrent Phase 2 trials for treatment of acute myeloid leukemia. Its therapeutic activity is dependent on maintenance of the synergistic 5:1 drug:drug ratio in vivo. CPX-351 liposomes have a mean diameter of 107 nm, a single phase transition temperature of 55.3 degrees C, entrapped volume of 1.5 microL/micromol lipid and a zeta potential of -33 mV. Characterization of these physicochemical properties led to identification of an internal structure within the liposomes, later shown to be produced during the cytarabine loading procedure. Fluorescence labeling studies are presented that definitively show that the structure is composed of lipid and represents a second lamella. Extensive spectroscopic studies of the drug-excipient interactions within the liposome and in solution reveal that interactions of both cytarabine and daunorubicin with the copper(II) gluconate/triethanolamine-based buffer system play a role in maintenance of the 5:1 cytarabine:daunorubicin ratio within the formulation. These studies demonstrate the importance of extensive biophysical study of liposomal drug products to elucidate the key physicochemical properties that may impact their in vivo performance.
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CPX-351 is based on the principle of ratiometric dosing of the cytarabine/daunorubicin combination with a molar ratio of 5:1, which provides the greatest synergistic effect with the lowest antagonism in vitro and in vivo.
“CPX-351 (Vyxeos) is a gel-phase bilamellar liposome nanoparticle with a mean diameter of 107 nm and a strong negative surface potential, which is based on the principle of ‘ratiometric’ dosing of the cytarabine/daunorubicin combination with a molar ratio of 5:1 provides the greatest synergistic effect with the lowest antagonism in vitro and in vivo.346”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [346]
CPX-351 (Vyxeos) is a gel-phase bilamellar liposome nanoparticle with a mean diameter of 107 nm and a strong negative surface potential.
“CPX-351 (Vyxeos) is a gel-phase bilamellar liposome nanoparticle with a mean diameter of 107 nm and a strong negative surface potential, which is based on the principle of ‘ratiometric’ dosing of the cytarabine/daunorubicin combination with a molar ratio of 5:1 provides the greatest synergistic effect with the lowest antagonism in vitro and in vivo.346”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [346]
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- Authors
- Dicko, A., Kwak, S., Frazier, A. A., Mayer, L. D., & Liboiron, B. D.
- Affiliations
- Celator Pharmaceuticals (Canada) (CA)
- Corresponding author
- Liboiron, Barry D.
- Venue
- International Journal of Pharmaceutics
- Publisher
- Elsevier BV
- Published
- 2010-05
- Volume
- 391
- Issue
- 1-2
- Pages
- 248-259
- ISSN
- 0378-5173 (ISSN-L)
- OpenAlex
- W2119367939
- Cited by
- 87
- References
- 35
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 12 · 2023: 10 · 2022: 8 · 2021: 2 · 2020: 9 · 2019: 5 · 2018: 9 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 3 · 2013: 2 · 2012: 5
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- Uppsala Universitet
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Keywords
- CPX-351, liposomal chemotherapy, cytarabine, daunorubicin, acute myeloid leukemia, liposome physicochemical properties, lipid bilayer structure, drug-excipient interaction, fluorescent labeling
- MeSH terms
- Buffers, Chemistry, Pharmaceutical, Cytarabine, Daunorubicin, Ethanolamines, Excipients, Gluconates, Liposomes, Particle Size, Transition Temperature
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