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The influence of Pluronics® on dark cytotoxicity, photocytotoxicity, localization and uptake of curcumin in cancer cells: studies of curcumin and curcuminoids XLIX

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Abstract

In order to apply curcumin as a photosensitizer in photodynamic therapy (PDT) one needs a formulation that can solubilize and stabilize the compound. Pluronics® (Pluronic) are reported to both solubilize and stabilize curcumin against hydrolytic degradation. The aim of the present work was therefore to investigate the influence of Pluronic formulation on the photocytotoxicity of curcumin. Interactions between curcumin and Pluronics were investigated by fluorescence emission and absorption spectroscopy. Cell survival was measured with the MTT assay. The location of curcumin in the cells was investigated with fluorescence microscopy, and the cellular uptake was measured with fluorescence emission spectroscopy. Pluronics P123 and F127 in contrast to Pluronic P85 and PEG 400 may solubilize curcumin under noncytotoxic conditions. An inverse relationship between the concentration of Pluronic and the photocytotoxicity of curcumin was observed. Curcumin could rapidly translocate across the cell membrane by passive diffusion. The fluorescence from curcumin in the cells (in the cytoplasm) after 1 hour of incubation was lowered by the presence of Pluronics in the formulation. However, the absolute amount of cell-bound curcumin after 1 hour of incubation was independent of the presence of Pluronics. Curcumin was bound more strongly to cells when incubated with formulations without Pluronics compared to cells incubated with curcumin formulations with Pluronics. Incubation of WiDr cells with curcumin for 6 hours resulted in lysosomal accumulation of curcumin independent of the presence of Pluronics. Lysosomally located curcumin could not be observed in HT1080 cells after 6 hours of incubation. The Pluronics P123 and F127 were found to be suitable for solubilizing and stabilizing curcumin, but inhibited photocytotoxic effects of curcumin unless the Pluronic concentration during treatment of the cells was less than 5–10× above the critical micellar concentration.

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References

  1. T. A. Dahl, P. Bilski, K. J. Reszka, C. F. Chignell, Photocytotoxicity of curcumin, Photochem. Photobiol., 1994, 59, 290–294.

    Article  CAS  Google Scholar 

  2. H. H. Tønnesen, J. Karlsen, Studies on curcumin and curcuminoids. VI. Kinetics of curcumin degradation in aqueous solution, Z. Lebensm.-Unters. Forsch., 1985, 180, 402–404.

    Article  Google Scholar 

  3. H. H. Tønnesen, M. Masson, T. Loftsson, Studies of curcumin and curcuminoids. XXVII. Cyclodextrin complexation: solubility, chemical and photochemical stability, Int. J. Pharm., 2002, 244, 127–135.

    Article  Google Scholar 

  4. H. H. Tønnesen, J. Karlsen, G. B. van Henegouwen, Studies on curcumin and curcuminoids. VIII. Photochemical stability of curcumin, Z. Lebensm.-Unters. Forsch., 1986, 183, 116–122.

    Article  Google Scholar 

  5. E. V. Batrakova, A. V. Kabanov, Pluronic block copolymers: evolution of drug delivery concept from inert nanocarriers to biological response modifiers, J. Controlled Release, 2008, 130, 98–106.

    Article  CAS  Google Scholar 

  6. FDA, Inactive Ingredient search for approved drug products, http://www.accessdata.fda.gov/scripts/cder/iig/index.cfm, Accessed 24.08.2009.

  7. E. Batrakova, S. Lee, S. Li, A. Venne, V. Alakhov, A. Kabanov, Fundamental relationships between the composition of Pluronic block copolymers and their hypersensitization effect in MDR cancer cells, Pharm. Res., 1999, 16, 1373–1379.

    Article  CAS  Google Scholar 

  8. R. Singh, S. Kristensen, H. H. Tønnesen, Influence of cosolvents, ionic strength and the method of sample preparation on the solubilization of curcumin by Pluronics and HP-?-cyclodextrin studies of curcumin and curcuminoids, XLIV, Pharmazie, 2012, 67, 131–142.

    CAS  PubMed  Google Scholar 

  9. H. H. Tønnesen, H. de Vries, J. Karlsen, G. Beijersbergen van Henegouwen, Studies on curcumin and curcuminoids. IX: investigation of the photobiological activity of curcumin using bacterial indicator systems, J. Pharm. Sci., 1987, 76, 371–373.

    Article  Google Scholar 

  10. E. M. Bruzell, E. Morisbak, H. H. Tønnesen, Studies on curcumin and curcuminoids. XXIX. Photoinduced cytotoxicity of curcumin in selected aqueous preparations, Photochem. Photobiol. Sci., 2005, 4, 523–530.

    Article  CAS  Google Scholar 

  11. T. Haukvik, E. Bruzell, S. Kristensen, H. H. Tønnesen, Photokilling of bacteria by curcumin in different aqueous preparations. Studies on curcumin and curcuminoids XXXVII, Pharmazie, 2009, 64, 666–673.

    CAS  Google Scholar 

  12. T. Haukvik, E. Bruzell, S. Kristensen, H. H. Tønnesen, Photokilling of bacteria by curcumin in selected polyethylene glycol 400 (PEG 400) preparations Studies on curcumin and curcuminoids, XLI, Pharmazie, 2010, 65, 600–606.

    CAS  PubMed  Google Scholar 

  13. A. B. Hegge, T. Andersen, J. E. Melvik, E. Bruzell, S. Kristensen, H. H. Tønnesen, Formulation and bacterial phototoxicity of curcumin loaded alginate foams for wound treatment applications: studies on curcumin and curcuminoides XLII, J. Pharm. Sci., 2011, 100, 174–185.

    Article  CAS  Google Scholar 

  14. A. Sahu, N. Kasoju, P. Goswami, U. Bora, Encapsulation of curcumin in Pluronic block copolymer micelles for drug delivery applications, J. Biomater. Appl., 2011, 25, 619–639.

    Article  CAS  Google Scholar 

  15. H. J. J. Pabon, Synthesis of curcumin and related compounds, Recl. J. R. Neth. Chem. Soc., 1964, 83, 379–386.

    CAS  Google Scholar 

  16. J. D. Stoien, R. J. Wang, Effect of near-ultraviolet and visible light on mammalian-cells in culture 2. Formation of toxic photoproducts in tissue-culture medium by blacklight, Proc. Natl. Acad. Sci. U. S. A., 1974, 71, 3961–3965.

    Article  CAS  Google Scholar 

  17. L. Nardo, R. Paderno, A. Andreoni, M. Masson, T. Haukvik, H. H. Tønnesen, Role of H-bond formation in the photoreactivity of curcumin, Spectrosc. Int. J., 2008, 22, 187–198.

    Article  CAS  Google Scholar 

  18. R. Nagarajan, Solubilization of hydrocarbons and resulting aggregate shape transitions in aqueous solutions of Pluronic (R) (PEO-PPO-PEO) block copolymers, Colloids Surf., B, 1999, 16, 55–72.

    Article  CAS  Google Scholar 

  19. H. Y. Cheng, W. W. Holl, Micellar aggregation of poloxamer 213 and its interaction with cholesterol derivatives, J. Pharm. Sci., 1990, 79, 907–912.

    Article  CAS  Google Scholar 

  20. A. Sahu, N. Kasoju, U. Bora, Fluorescence study of the curcumin-casein micelle complexation and its application as a drug nanocarrier to cancer cells, Biomacromolecules, 2008, 9, 2905–2912.

    Article  CAS  Google Scholar 

  21. A. Sahu, U. Bora, N. Kasoju, P. Goswami, Synthesis of novel biodegradable and self-assembling methoxy poly(ethylene glycol)-palmitate nanocarrier for curcumin delivery to cancer cells, Acta Biomater., 2008, 4, 1752–1761.

    Article  CAS  Google Scholar 

  22. W. W. Quitschke, Differential solubility of curcuminoids in serum and albumin solutions: implications for analytical and therapeutic applications, BMC Biotechnol., 2008, 8.

    Google Scholar 

  23. P. H. Bong, Spectral and photophysical behaviors of curcumin and curcuminoids, Bull. Korean Chem. Soc., 2000, 21, 81–86.

    CAS  Google Scholar 

  24. C. Guo, J. Wang, X. Liang, L. Zheng, H. Liu, Effect of bovine serum albumin on the micellization of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymers in aqueous solutions by fluorescence spectroscopy, Sci. China, Ser. B: Chem., 2006, 49, 541–549.

    Article  CAS  Google Scholar 

  25. M. Svensson, K. Berggren, A. Veide, F. Tjerneld, Aqueous two-phase systems containing self-associating block copolymers–partitioning of hydrophilic and hydrophobic biomolecules, J. Chromatogr., A, 1999, 839, 71–83.

    Article  CAS  Google Scholar 

  26. T. Minko, E. V. Batrakova, S. Li, Y. L. Li, R. I. Pakunlu, V. Y. Alakhov, A. V. Kabanov, Pluronic block copolymers alter apoptotic signal transduction of doxorubicin in drug-resistant cancer cells, J. Controlled Release, 2005, 105, 269–278.

    Article  CAS  Google Scholar 

  27. E. V. Batrakova, S. Li, W. F. Elmquist, D. W. Miller, V. Y. Alakhov, A. V. Kabanov, Mechanism of sensitization of MDR cancer cells by Pluronic block copolymers: selective energy depletion, Br. J. Cancer, 2001, 85, 1987–1997.

    Article  CAS  Google Scholar 

  28. E. V. Batrakova, S. Li, S. V. Vinogradov, V. Y. Alakhov, D. W. Miller, A. V. Kabanov, Mechanism of pluronic effect on P-glycoprotein efflux system in blood–brain barrier: contributions of energy depletion and membrane fluidization, J. Pharmacol. Exp. Ther., 2001, 299, 483–493.

    CAS  PubMed  Google Scholar 

  29. A. V. Kabanov, E. V. Batrakova, S. Li, V. Y. Alakhov, Selective energy depletion and sensitization of multiple drug-resistant cancer cells by pluronic block copolymer, Macromol. Symp., 2001, 172, 103–112.

    Article  CAS  Google Scholar 

  30. D. Y. Alakhova, N. Y. Rapoport, E. V. Batrakova, A. A. Timoshin, S. Li, D. Nicholls, V. Y. Alakhov, A. V. Kabanov, Differential metabolic responses to pluronic in MDR and non-MDR cells: a novel pathway for chemosensitization of drug resistant cancers, J. Controlled Release, 2010, 142, 89–100.

    Article  CAS  Google Scholar 

  31. E. V. Batrakova, S. Li, V. Y. Alakhov, D. W. Miller, A. V. Kabanov, Optimal structure requirements for Pluronic block copolymers in modifying P-glycoprotein drug efflux transporter activity in bovine brain microvessel endothelial cells, J. Pharmacol. Exp. Ther., 2003, 304, 845–854.

    Article  CAS  Google Scholar 

  32. Z. Wei, S. Yuan, Y. Chen, S. Yu, J. Hao, J. Luo, X. Sha, X. Fang, Enhanced antitumor efficacy by Paclitaxel-loaded Pluronic P123/F127 mixed micelles against non-small cell lung cancer based on passive tumor targeting and modulation of drug resistance, Eur. J. Pharm. Biopharm., 2010, 75, 341–353.

    Article  Google Scholar 

  33. A. P. Castano, T. N. Demidova, M. R. Hamblin, Mechanisms in photodynamic therapy: part one-photosensitizers, photochemistry and cellular localization, Photodiagn. Photodyn. Ther., 2005, 1, 279–293.

    Article  Google Scholar 

  34. A. Kunwar, A. Barik, B. Mishra, K. Rathinasamy, R. Pandey, K. I. Priyadarsini, Quantitative cellular uptake, localization and cytotoxicity of curcumin in normal and tumor cells, Biochim. Biophys. Acta, Gen. Subj., 2008, 1780, 673–679.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. School of Pharmacy, Department of Pharmaceutics, University of Oslo, P.O. Box 1068, Blindern, 0316, Oslo, Norway

    Ravinder Singh, Hanne Hjorth Tønnesen, Solveig Kristensen & Kristian Berg

  2. Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway

    Kristian Berg

Authors
  1. Ravinder Singh
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  2. Hanne Hjorth Tønnesen
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  3. Solveig Kristensen
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  4. Kristian Berg
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Correspondence to Ravinder Singh.

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† Electronic supplementary information (ESI) available. See DOI: 10.1039/c2pp25249j

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Singh, R., Tønnesen, H.H., Kristensen, S. et al. The influence of Pluronics® on dark cytotoxicity, photocytotoxicity, localization and uptake of curcumin in cancer cells: studies of curcumin and curcuminoids XLIX. Photochem Photobiol Sci 12, 559–575 (2013). https://doi.org/10.1039/c2pp25249j

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