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Versatile Fixed-Ratio Drug Combination Delivery Using Hydrophobic Prodrug Nanoparticles

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Multifunctional Nanoparticles for Drug Delivery Applications

Part of the book series: Nanostructure Science and Technology ((NST))

Abstract

The current paradigm of cancer chemotherapy involves the co-administration of multiple anticancer agents at their maximum tolerated doses to achieve greater antitumor activity than could be realized with single agents alone. Emerging evidence, however, points to the important role drug ratios play in determining whether in vivo drug interactions are synergistic or antagonistic in nature. The CombiPlex® technology platform was developed to deliver multiple chemotherapy drugs at a defined synergistic drug ratio via a particulate carrier. The promising clinical results of CPX-351 in the treatment of newly diagnosed acute myelogenous leukemia (AML) serve as an example of the magnitude of gains that can be made when combination chemotherapy drugs are delivered to the target site at their synergistic ratio. While the CombiPlex technology had been used to develop three clinical and preclinical liposomal products, there have been several reports of drug combinations formulated into polymer-based nanoparticles, typically involving hydrophobic drugs which are not generally suitable for liposome encapsulation.

In this chapter, the rationale for delivering drug combinations at defined ratios is discussed using CPX-351 as an example formulation, one that delivers drugs to the target site and maintains the formulated drug ratio in vivo. Dual drug nanoparticle formulations are then evaluated on their ability to maintain the molar ratio of the two loaded drugs. Finally, we discuss the extension of the CombiPlex approach to drug combinations of disparate physicochemical properties through preparation and nanoparticle encapsulation of drug conjugates.

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  1. Celator Pharmaceuticals Corp., 1779 West 75th Avenue, Vancouver, BC, Canada, V6P 6P2

    Barry D. Liboiron, Paul G. Tardi & Lawrence D. Mayer

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  1. Barry D. Liboiron
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  2. Paul G. Tardi
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  3. Lawrence D. Mayer
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Correspondence to Lawrence D. Mayer .

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  1. Drug Delivery Solutions LLC, Temple Street 16, Arlington, 02476, Massachusetts, USA

    Sonke Svenson

  2. Princeton University, n/a, Princeton, 08544, USA

    Robert K. Prud'homme

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Liboiron, B.D., Tardi, P.G., Mayer, L.D. (2012). Versatile Fixed-Ratio Drug Combination Delivery Using Hydrophobic Prodrug Nanoparticles. In: Svenson, S., Prud'homme, R. (eds) Multifunctional Nanoparticles for Drug Delivery Applications. Nanostructure Science and Technology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-2305-8_6

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