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Liposomes for Solubilization and Delivery of Curcumin into Leukemia Cells

  • Jang, Rae-Sung (School of Life Sciences and Biotechnology, Korea University) ;
  • Kim, Eun-Joong (School of Pharmacy, Seoul National University) ;
  • Suh, Min-Sung (School of Life Sciences and Biotechnology, Korea University) ;
  • Shim, Ga-Yong (School of Life Sciences and Biotechnology, Korea University) ;
  • Shim, Chang-Koo (School of Pharmacy, Seoul National University) ;
  • Oh, Yu-Kyoung (School of Life Sciences and Biotechnology, Korea University)
  • Published : 2006.10.21

Abstract

Curcumin is a phytochemical compound with anticancer activity. Although curcumin has substantial pharmacological effect against various cancers, the low solubility of curcumin has hindered its development. For an organic solvent-free injectable formulation, we encapsulated curcumin in various liposomes. Due to its lipophilic property, curcumin was placed in the membrane region of liposomes. Curcumin was stably encapsulated in all formulations tested in this study. The cellular uptake of curcumin delivered in liposomal formulations or free form was measured in K562 human leukemia cell lines using a flow cytometry and MTT viability assay, respectively. Although all the liposomes could solubilize curcumin, the cellular levels and the anticancer effects of liposomal curcumin varied with the composition of liposomes. Moreover, liposomal curcumin down-regulated the expression of Notch-1, the molecule involved in the carcinogenesis, to the similar extent to free curcumin dissolved in dimethyl sulfoxide. These results warrant the development of liposomal curcumin as an injectable formulation for leukemia treatment.

References

  1. A.L. Cheng, C.H. Hsu, J.K. Lin, M.M. Hsu, Y.K. Ho, T.S. Shen, J.Y. Ko, J.T. Lin, B.R. Lin, W. Ming-Shiang, H.S. Yu, S.H. Jee, G.S. Chen, T.M. Chen, C.A. Chen, M.K. Lai, Y.S. Pu, M.H. Pan, Y.J. Wang, C.C Tsai and C.Y. Hsieh, Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions, Anticancer Res., 21, 2895-2900 (2001)
  2. M. Roy, S. Chakraborty, M. Siddiqi and R.K. Bhattacharya, Induction of apoptosis in tumor cells by natural phenolic compounds, Asian Pac. J. Cancer Prev., 3, 61-67 (2002)
  3. S. Fiorucci, R. Meli, M. Bucci and G. Cirino, Dual inhibitors of cyclooxygenase and 5-lipoxygenase. A new avenue in anti-inflammatory therapy?, Biochem. Pharmacol., 62, 1433-1438 (2001) https://doi.org/10.1016/S0006-2952(01)00747-X
  4. A. Duvoix, S. Delhalle, R. Blasius, M. Schnekenburger, F. Morceau, M. Fougere, E. Henry, M. Galteau, M. Dicato and M. Diederich, Effect of chemopreventive agents on glutathione S-transferase P1-1 gene expression mechanisms via activating protein 1 and nuclear factor kappaB inhibition, Biochem. Pharmacol., 68, 1101-1111 (2004) https://doi.org/10.1016/j.bcp.2004.05.001
  5. A. Duvoix, R. Blasius, S. Delhalle, M. Schnekenburger, F. Morceau, E. Henry, M. Dicato and M. Diederich, Chemopre- ventive and therapeutic effects of curcumin, Cancer Lett., 223, 181-190 (2005) https://doi.org/10.1016/j.canlet.2004.09.041
  6. Y.J. Surh, S.S. Han, Y.S. Keum, H.J. Seo and S. S. Lee, Inhibitory effects of curcumin and capsaicin on phorbol esterinduced activation of eukaryotic transcription factors, NF-kappaB and AP-1, Biofactors, 12, 107-112 (2000) https://doi.org/10.1002/biof.5520120117
  7. R.J. Anto, A. Mukhopadhyay, K. Denning and B.B. Aggarwal, Curcumin (diferuloylmethane) induces apoptosis through activation of caspase-8, BID cleavage and cytochrome c release: its suppression by ectopic expression of Bcl-2 and Bcl-xl, Carcinogenesis, 23, 143-150 (2002) https://doi.org/10.1093/carcin/23.1.143
  8. A. Kunwar, A. Barik, R. Pandey and K. I. Priyadarsini, Transport of liposomal and albumin loaded curcumin to living cells: an absorption and fluorescence spectroscopic study, Biochim. Biophys. Acta, in press (2006)
  9. L.T. Lam, C. Ronchini, J. Norton, A.J. Capobianco and E.H. Bresnick, Suppression of erythroid but not megakaryocytic differentiation of human K562 erythroleukemic cells by Notch-1, J. Biol. Chem., 275, 19676-19684 (2000) https://doi.org/10.1074/jbc.M002866200
  10. Z. Wang, Y. Zhang, S. Banerjee, Y. Li and F.H. Sarkar, Notch-1 down-regulation by curcumin is associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells, Cancer, 106, 2503-2513 (2006) https://doi.org/10.1002/cncr.21904
  11. P. Sapra and T.M. Allen, Ligand-targeted liposomal anticancer drugs, Prog. Lipid Res., 42, 439-462 (2003) https://doi.org/10.1016/S0163-7827(03)00032-8