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Enhancement of Curcumin Bioavailability Via the Prodrug Approach: Challenges and Prospects

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Abstract

Curcumin is a natural product with many interesting pharmacological properties. However, these are offset by the particularly poor biopharmaceutical properties. The oral bioavailability of curcumin in humans is very low, mainly due to low solubility, poor stability, and extensive metabolism. This has led to multiple approaches to improve bioavailability, including administration of curcumin with metabolism inhibitors, formulation into nanoparticles, modification of the curcumin structure, and development of curcumin prodrugs. In this paper, we focus on the pharmacokinetic outcomes of these approaches. Pharmacokinetic parameters of curcumin after release from prodrugs are dependent on the linker between curcumin and the promoiety, and the release itself may depend on the physiological and enzymatic environment at the site of cleavage. This is an area in which more data are required for rational design of improved linkers. Cytotoxicity of curcumin prodrugs seems to correlate well with cellular uptake in vitro, but the in vivo relevance is uncertain. We conclude that improved experimental and theoretical models of absorption of curcumin prodrugs, development of accurate analytical methods for simultaneous measurement of plasma levels of prodrug and released curcumin, and acquisition of more pharmacokinetic data in animal models for dose prediction in humans are required to facilitate movement of curcumin prodrugs into clinical trials.

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Authors and Affiliations

  1. Biomedicinal Chemistry Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phayathai Road, Patumwan, Bangkok, 10330, Thailand

    Pahweenvaj Ratnatilaka Na Bhuket

  2. Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA, USA

    Asma El-Magboub & Ian S. Haworth

  3. Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phayathai Road, Patumwan, Bangkok, 10330, Thailand

    Pornchai Rojsitthisak

Authors
  1. Pahweenvaj Ratnatilaka Na Bhuket
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  2. Asma El-Magboub
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  3. Ian S. Haworth
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  4. Pornchai Rojsitthisak
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Correspondence to Pornchai Rojsitthisak.

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Funding

The preparation of this manuscript was supported by the Annual Research Fund of the Faculty of Pharmaceutical Sciences, Chulalongkorn University (P. Rojsitthisak), the Ratchadapiseksompoch Endowment Fund of Chulalongkorn University (CU-58-003-HR and CU-59-031-AM) (P. Rojsitthisak), the National Research University Project, Office of Higher Education Commission (NRU59-047-AM) (P. Rojsitthisak) and the scholarship from the Graduate School, Chulalongkorn University to commemorate the 72nd anniversary of his Majesty King Bhumibala Aduladeja (P. Ratnatilaka Na Bhuket).

Conflicts of interest

Pahweenvaj Ratnatilaka Na Bhuket, Asma El-Magboub, Ian S. Haworth and Pornchai Rojsitthisak declare no conflict of interest.

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Ratnatilaka Na Bhuket, P., El-Magboub, A., Haworth, I.S. et al. Enhancement of Curcumin Bioavailability Via the Prodrug Approach: Challenges and Prospects. Eur J Drug Metab Pharmacokinet 42, 341–353 (2017). https://doi.org/10.1007/s13318-016-0377-7

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  • DOI: https://doi.org/10.1007/s13318-016-0377-7

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