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Platinum-Based Antitumor Drugs and Their Liposomal Formulations in Clinical Trials

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Abstract

Platinum-based antitumor drugs are the most common drugs in modern oncology practice. They are used for the treatment of a large number of malignant tumors of different etiology. However, their low specificity and high systemic toxicity significantly reduce the efficacy of chemotherapy. With the goal of improving pharmacological properties of platinum-based drugs, an intense search for supramolecular drug delivery systems is being carried out in many laboratories. This review focuses on liposomal drugs, which are currently at different stages of clinical trials. In the first part of the review we described modern concepts on the action of Pt-based drugs. Information about the drugs used in clinical practice as well as data about some new promising compounds is also provided. Also, justification of the rationale for the creation of liposomal drug delivery systems is given, and six Pt-containing liposomal formulations under clinical trials are reviewed, including the published data on the composition, how they act, and the results of preclinical and clinical trials. Several examples of new Pt-based liposomal formulations are given. The prospects of the liposomal platform development for platinum-based drugs are discussed.

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Abbreviations

DPPG:

1,2-dipalmitoyl-sn-glycero-3-phosphorac-( 1-glycerol) sodium salt

DSPC:

1,2-distearoyl-SN-glycero-3-phosphocholine

DSPG:

1,2-distearoyl-sn-glycero-3-phospho-rac-(1-glycerol) sodium salt

DMPC:

1,2-dimiristoyl-SN-glycero-3-phosphocholine

DMPG:

1,2-dimiristoyl-snglycero-3-phospho-rac-(1-glycerol) sodium salt

EPR:

enhanced permeability and retention effect

HSPC:

hydrogenated soybean phosphatidylcholine

MTD:

maximum tolerated dose

PEG:

polyethylene glycol

PEG-PE:

1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]

RES:

reticuloendothelial system

AUC:

area under the curve “concentration-time;” NDDP, cis-bis-neodecanoate-trans-R,R-1,2-diaminocyclohexane platinum(II)

SPC:

soybean phosphatidylcholine

NA:

not available

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Authors and Affiliations

  1. Drugs Technology Ltd., Khimki, Мoscow, 141400, Russia

    D. A. Arantseva

  2. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia

    E. L. Vodovozova

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  1. D. A. Arantseva
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The manuscript is based on the report presented at the conference “Lipids of the XXI Century. First Quarter,” October 22–23, 2018, Moscow.

Original Russian Text © D.A. Arantseva, E.L. Vodovozova, 2018, published in Bioorganicheskaya Khimiya, 2018, Vol. 44, No. 6, pp. 620–632.

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Arantseva, D.A., Vodovozova, E.L. Platinum-Based Antitumor Drugs and Their Liposomal Formulations in Clinical Trials. Russ J Bioorg Chem 44, 619–630 (2018). https://doi.org/10.1134/S1068162018060031

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