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Bioavailability of silymarin flavonolignans: drug formulations and biotransformation

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Abstract

Over the past years, great advances have been made on the development of novel delivery systems for bioactive natural compounds, in parallel to their structural modification via chemical, chemo-enzymatic and enzymatic methodologies. These approaches give rise to novel formulations and derivatives that often display advantages over the parental molecule, such as enhanced bioavailability and pharmacological activity, due to improved dissolution and stability. Silymarin components suffer from poor solubility in water and lipid media and their resorption in the intestine is rather limited. Moreover, silybin undergoes intensive Phase II metabolism and is rapidly excreted in bile and urine, leading to low therapeutic efficacy. This work aims to present the current status of available silymarin formulations, and to highlight successful efforts for the biotransformation of its constituent flavonolignans towards the synthesis of novel derivatives. Herein, various pharmaceutical formulations that aim at the bioavailability improvement of these fascinating phytochemicals, i.e., liposomes, phytosomes, self-microemulsifying drug delivery systems, solid dispersions systems, dripping pills, nanosuspensions, floating tablets, and micronization, are reviewed. Silybin (semi)synthetic derivatives prepared by chemical or enzymatic methods, such as fatty acid conjugates, silybin bishemisuccinate, silybin glycosides, silybin sulfates, silybinic acid, and 2,3-dehydrosilybin, are also discussed in detail. Additionally, this work attempts to direct the attention towards the pharmacological implications of optically pure silybin A and silybin B and their biotransformation reactions, both Phase I and II, in relation to bioavailability.

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Abbreviations

CYP:

Cytochrome P450

DPPH:

2,2-Diphenyl-1-picrylhydrazyl

GI:

Gastrointestinal

GST:

Glutathione S-transferase

MDA:

Malonaldehyde

PEG:

Polyethylene glycol

Pgp:

P–glycoprotein

ROS:

Reactive oxygen species

SEDDS:

Self emulsifying drug delivery system

SMEDDS:

Self-micro emulsifying drug delivery system

UDP:

Uridine diphosphate

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Acknowledgments

This work was supported by the grant from the Czech Science Foundation P301/11/0662; ESF COST Chemistry CM0804 (MŠMT LD11051 and ME10027).

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  1. Eleni Theodosiou

    Present address: Laboratory of Chemical Biotechnology, Department of Biochemical and Chemical Engineering, TU Dortmund, Emil-Figge-Strasse 66, 44227, Dortmund, Germany

Authors and Affiliations

  1. Biotechnology Laboratory, Chemical Engineering Department, National Technical University of Athens, Athens, Greece

    Eleni Theodosiou & Fragiskos Kolisis

  2. Laboratory of Biotransformation, Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, 14220, Prague 4, Czech Republic

    Kateřina Purchartová & Vladimír Křen

  3. Laboratory of Biotechnology, Department of Biological Applications and Technologies, University of Ioannina, Ioannina, Greece

    Haralambos Stamatis

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Theodosiou, E., Purchartová, K., Stamatis, H. et al. Bioavailability of silymarin flavonolignans: drug formulations and biotransformation. Phytochem Rev 13, 1–18 (2014). https://doi.org/10.1007/s11101-013-9285-5

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  • DOI: https://doi.org/10.1007/s11101-013-9285-5

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