Stabilisation of Curcumin for Delivery Inside Live Cell

Curcumin, widely used as spice in Asia is found in rhizome of turmeric plant (Curcuma longa and Curcuma xanthorrhiza). It shows antibacterial, anti-inflammatory, hypoglycemic, antioxidant, antimicrobial activities and capable of treating fatal disease like cancer, Parkinson’s disease. It is highly unstable in aqueous solution specially in high pH condition makes it deceptively useful. In this this review we have shown several techniques and schemes that made curcumin a potent useful drug. Forming complex with proteins, lipids, lipoproteins, cyclodextrin and bio-mimicking molecules is effective to increase bioavailability of this hydrophobic molecule. Nature of interactions and binding mechanism with those molecules are discussed here. Most important aspect of this review is to deliver curcumin inside live cells and finding the effects on cell death (apoptosis) and proliferations. Different drug delivery systems have been developed which show excellent rate of internalisation. Curcumin has been delivered intravenously in live mouse model.

Curcumin, Internalisation, Bio availability, Drug delivery, Proliferation

1. A Goel, A. B. Kunnumakkara, B. B. Aggarwal. “Curcumin as “Curecumin”: from kitchen to clinic,” Biochem. Pharmacol 75 (2008): 787−809. [Google Scholar] [Crossref]

2. G. Bar-Sela, R. Epelbaum, M. Schaffer, “Curcumin as an anti-cancer agent: review of the gap between basic and clinical applications,” Curr Med Chem. 17 (2010): 190-197. [Google Scholar] [Crossref]

3. J. S. Jurenka, “Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research,” Altern. Med. Rev.14 (2009): 141-153. [Google Scholar] [Crossref]

4. R. K. Maheshwari, A. K. Singh, J. Gaddipati, R. C. Srimal, “Multiple biological activities of curcumin: a short review,” Life Sci. 78 (2006): 2081-2087. [Google Scholar] [Crossref]

5. A. S. Strimpakos, R. A. Sharma, “Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials,” Antioxid. Redox Signal 10 (2008): 511-545. [Google Scholar] [Crossref]

6. R. A. Sharma, W. P. Steward, A. J. Gescher, “Pharmacokinetics and pharmacodynamics of curcumin,” Adv. Exp. Med. Biol. 595 (2007): 453-470. [Google Scholar] [Crossref]

7. A. Krishnamoorthy 1950. The wealth of India: a dictionary of indian raw materials and industrial products. Vol. 2, p. 402. CSIR, New Delhi. [Google Scholar] [Crossref]

8. O. P. Sharma, “Antioxidant activity of curcumin and related compounds,” Biochem. Pharmacol. 25 (1976): 1811–1812. [Google Scholar] [Crossref]

9. N. Sreejayan, T. P. A. Devasagayam, K. I. Priyadarsini, M. N. A. Rao, “Inhibition of radiation induced lipid peroxidation by curcumin,” Int. J. Pharmacol. 151 (1997): 127–130. [Google Scholar] [Crossref]

10. K. I. Priyadarsini, “Free radical reaction of curcumin in membrane models,” Free Radic. Biol. Med. 23, no. 6 (1997): 838–843. [Google Scholar] [Crossref]

11. S. M. Khopde, K. I. Priyadarsini, P. Venkatesan, M. N. A. Rao, “Free radical scavenging ability and antioxidant efficiency of curcumin and its substituted analogue,” Biophys. Chem. 80 (1999): 85–91. [Google Scholar] [Crossref]

12. G. M. Cole, B. Teter, S. A. Frautschy,. “Curcumin as ″Curecumin″: from kitchen to clinic,” Adv. Exp. Med. Biol. 595 (2007): 197− 212. [Google Scholar] [Crossref]

13. G. P. Lim, T. Chu, F. S. Yang, W. Beech, S. A. Frautschy, G. M. Cole, “The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse,” J. Neurosci. 21 (2001): 8370−8377. [Google Scholar] [Crossref]

14. FYang, G. P. Lim, A. N. Begum, O. J. Ubeda, M. R. Simmons, S. S. Ambegaokar, P. P. Chen, R. Kayed, C. G. Glabe, S. A. Frautschy, G. M. Cole, “Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo,” J. Biol. Chem. 280 (2005): 5892−5901. [Google Scholar] [Crossref]

15. G. Khuwaja, M. M. Khan, T. Ishrat, A. Ahmad, S. S. Raza, M. Ashafaq, H. Javed, M. B. Khan, A. Khan, K. Vaibhav, M. M. Safhi, F. Islam, “Neuroprotective effects of curcumin on 6- hydroxydopamine-induced Parkinsonism in rats: behavioral, neuro- chemical and immunohistochemical studies,” Brain Res. 1368 (2011): 254−263. [Google Scholar] [Crossref]

16. M. A. Hickey, C. Zhu, V. Medvedeva, R. P. Lerner, S. Patassini, N. R. Franich, P. Maiti, S. A. Frautschy, S. Zeitlin, M. S. Levine, M. F. Chesselet, “Improvement of neuropathology and transcriptional deficits in CAG 140 knock-in mice supports a beneficial effect of dietary curcumin in Huntington’s disease,” Mol. Neurodegener. 7 (2012): 12. [Google Scholar] [Crossref]

17. Y. J. Wang, M. H. Pan, A. L. Cheng, L. I. Lin, Y. S. Ho, C. Y. Hsieh, J. K. Lin, “Stability of curcumin in buffer solutions and characterization of its degradation products,” J. Pharm. Biomed. Anal. 15 (1997): 1867-1876. [Google Scholar] [Crossref]

18. P. Anand, A. B. Kunnumakkara, R. A. Newman, B. B. Aggarwal,. “Bioavailability of curcumin: problems and promises,” Mol. Pharm. 4 (2007): 807-818. [Google Scholar] [Crossref]

19. A. L. Cheng, C. H. Hsu, J. K. Lin, M. M. Hsu, Y. F. 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, C. Y. Hsieh, “Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions,” Anticancer Res. 21 (2001): 2895–2900. [Google Scholar] [Crossref]

20. N. Dhillon, B. B. Aggarwal, R. A. Newman, R. A. Wolff, A. B. Kunnumakkara, J. L. Abbruzzese, C. S. Ng, V. Badmaev, R. Kurzrock, “Phase II trial of curcumin in patients with advanced pancreatic cancer,” Clin. Cancer Res. 14 (2008): 4491–4499. [Google Scholar] [Crossref]

21. K. I. Priyadarsini, “Photophysics, photochemistry and photobiology of curcumin: Studies from organic solutions, bio-mimetics and living cells,” J. Photochem. and Photobio. C: Photochem. Rev. 10 (2009): 85-91. [Google Scholar] [Crossref]

22. M. Ghosh, N. Sarkar, “Exploring the World of Curcumin: Photophysics, Photochemistry, and Applications in Nanoscience and Biology,” ChemBioChem. 25, no. 23 (2024): e202400335. [Google Scholar] [Crossref]

23. N. Bera, S. Layek, S. Pramanik, P. K. Nandi, R. Hazra, N. Sarkar, “Ultrafast Dynamics of the Medicinal Pigment Curcumin inside the Imidazolium Surface Active Ionic Liquid Containing Giant Vesicles and White Light Generation via Triple-FRET Technique,” Langmuir 39 (2023): 11653−11663. [Google Scholar] [Crossref]

24. Mandal S, Banerjee C, Ghosh S, Kuchlyan J, Sarkar N. 2013. Modulation of the Photophysical Properties of Curcumin in Nonionic Surfactant (Tween-20) Forming Micelles and Niosomes: A Comparative Study of Different Microenvironments. J. Phys. Chem. B. 117 (23): 6957–6968 [Google Scholar] [Crossref]

25. M. M. Yallapua, M. Jaggi, S. C. Chauhana, “β-Cyclodextrin-curcumin self-assembly enhances curcumin delivery in prostate cancer cells,” Colloids Surf. B: Biointerfaces 79 (2010): 113–125. [Google Scholar] [Crossref]

26. Harada T, Pham D, Leung M. H. M, Ngo H. T, Lincoln S. F, Easton C. J, Kee T. W. 2011. Cooperative Binding and Stabilization of the Medicinal Pigment Curcumin by Diamide Linked γ-Cyclodextrin Dimers: A Spectroscopic Characterization. J. Phys. Chem. B. 115: 1268–1274. [Google Scholar] [Crossref]

27. T. Harada, H. L. Mc Ternan, D. Pham, S. F. Lincoln, T. W. Kee “Femtosecond Transient Absorption Spectroscopy of the Medicinal Agent Curcumin in Diamide Linked γ‑Cyclodextrin Dimers,” J. Phys. Chem. B 119 (2015): 2425−2433. [Google Scholar] [Crossref]

28. A. Gupta, S. M. Briffa, S. Swingler, H. Gibson, V. Kannappan, G. Adamus, M. Kowalczuk, C. Martin, I. Radecka, “Synthesis of Silver Nanoparticles Using Curcumin-Cyclodextrins Loaded into Bacterial Cellulose-Based Hydrogels for Wound Dressing Applications,” Biomacromolecules 21 (2020): 1802−1811. [Google Scholar] [Crossref]

29. F. Zsila, Z. Bikádi, M. Simonyi, “Unique, pH-dependent biphasic band shape of the visible circular dichroism of curcumin–serum albumin complex,” Biochem. Biophys. Res. Commun. 301 (2003): 776–782. [Google Scholar] [Crossref]

30. F. Zsila, Z. Bika ´di, M. Simonyi, “Molecular basis of the Cotton effects induced by the binding of curcumin to human serum albumin,” Tetrahedron Asym. 14 (2003): 2433–2444. [Google Scholar] [Crossref]

31. M. Maciazek-Jurczyk, M. Maliszewska, J. Pozycka, J. Równicka-Zubik, A. Góra, A. Sułkowska, “Tamoxifen and curcumin binding to serum albumin. Spectroscopic study” J. Mol. Struct. 1044 (2013): 194–200. [Google Scholar] [Crossref]

32. D. Patra, C. Barakat, R. M. Tafech, “Study on effect of lipophilic curcumin on sub-domain IIA site of human serum albumin during unfolded and refolded states: A synchronous fluorescence spectroscopic study,” Colloids Surf. B: Biointerfaces 94 (2012): 354– 361. [Google Scholar] [Crossref]

33. M. H. M. Leung, T. W. Kee, “Effective Stabilization of Curcumin by Association to Plasma Proteins: Human Serum Albumin and Fibrinogen,” Langmuir 25, no.10 (2009): 5773–5777. [Google Scholar] [Crossref]

34. P. K. Singh, V. Kotia, D. Ghosh, G. M. Mohite, A. Kumar, S. K. Maji, “Curcumin Modulates α‑Synuclein Aggregation and Toxicity,” ACS Chem. Neurosci. 4 (2013): 393−407. [Google Scholar] [Crossref]

35. A. Kunwar, A. Barik, R. Pandey, K. I. Priyadarsini, “Transport of liposomal and albumin loaded curcumin to living cells: An absorption and fluorescence spectroscopic study,” Biochim. Biophys. Acta. 1760 (2006): 1513– 1520. [Google Scholar] [Crossref]

36. M. Fatemizadeh, F. Tafvizi, F. Shamsi, S. Amiri, A. Farajzadeh, I. Akbarzadeh, “Apoptosis Induction, Cell Cycle Arrest and Anti-Cancer Potential of Tamoxifen-Curcumin Loaded Niosomes Against MCF-7 Cancer Cells,” Iran J. Pathol. 17, no.2 (2022): 183- 190. [Google Scholar] [Crossref]

37. T. Harada, L. Giorgio, T. J. Harris, D. Pham, H. T. Ngo, E. F. Need, B. J. Coventry, S. F. Lincoln, C. J. Easton, G. Buchanan, T. W. Kee, “Diamide Linked γ‑Cyclodextrin Dimers as Molecular-Scale Delivery Systems for the Medicinal Pigment Curcumin to Prostate Cancer Cells,” Mol. Pharmaceutics. 10 (2013): 4481−4490. [Google Scholar] [Crossref]

38. 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. 1780 (2008): 673– 679. [Google Scholar] [Crossref]

39. A. Safavy, K. P. Raisch, S. Mantena, L. L. Sanford, S. W. Sham, N. R. Krishna, J. A. Bonner, “Design and Development of Water-Soluble Curcumin Conjugates as Potential Anticancer Agents,” J. Med. Chem. 50 (2007): 6284 - 6288. [Google Scholar] [Crossref]

40. K. Sou, S. Inenaga, S. Takeoka, E. Tsuchida “Loading of curcumin into macrophages using lipid-based nanoparticles,” Int. J. Pharm. 352 (2008): 287–293 [Google Scholar] [Crossref]

41. B. Lu, Y. Zhong, J. Zhang,. “Curcumin-Based Ionic Liquid Hydrogel for Topical Transdermal Delivery of Curcumin To Improve Its Therapeutic Effect on the Psoriasis Mouse Model,” ACS Appl. Mater. Interfaces 16, no. 14 (2024): 17080 – 17091. [Google Scholar] [Crossref]

42. I. A. Bhat, R. Jain, M. M. Siddiqui, D. K. Saini, P. S. Mukherjee, “Water-Soluble Pd8L4 Self-assembled Molecular Barrel as an Aqueous Carrier for Hydrophobic Curcumin,” Inorg. Chem. 56 (2017): 5352−5360. [Google Scholar] [Crossref]

43. S. Bisht, G. Feldmann, S. Soni, R. Ravi, C. Karikar, A. Maitra, “Polymeric nanoparticle-encapsulated curcumin (“nanocurcumin"): a novel strategy for human cancer therapy,” J. Nanobiotechnol. 5 (2007): 3. [Google Scholar] [Crossref]

44. S. K. Yadava, S. M. Basu, R. Valsalakumari, M. Chauhan, M. Singhania, J. Giri, “Curcumin-Loaded Nanostructure Hybrid Lipid Capsules for Co-eradication of Breast Cancer and Cancer Stem Cells with Enhanced Anticancer Efficacy,” ACS Appl. Bio Mater. 3, no. 10 (2020): 6811–6822. [Google Scholar] [Crossref]

45. S. Patra, J. Dey, A. Chakraborty, “Physicochemical Characterization, Stability, and In Vitro Evaluation of Curcumin-Loaded Solid Lipid Nanoparticles Prepared Using Biocompatible Synthetic Lipids,” ACS Appl. Bio Mater. 6 (2023): 2785−2794. [Google Scholar] [Crossref]

46. S. Hajigholami, Z. V. Malekshahi, N. Bodaghabadi, F. Najafi, H. Shirzad, M. Sadeghizadeh “Nano Packaged Tamoxifen and Curcumin; Effective Formulation against Sensitive and Resistant MCF-7 Cells,” Iran. J. Pharm. Res. 17, no. 1 (2018): 1-10. [Google Scholar] [Crossref]

47. J. Chae, Y. Choi, J. Hong, N. Kim, J. Kim, H. Y. Lee, J. Choi “Anti cancer and Antibacterial Properties of Curcumin-Loaded Mannosylated Solid Lipid Nanoparticles for the Treatment of Lung Disease,” ACS Appl. Bio Mater. 7 (2024): 2175−2185. [Google Scholar] [Crossref]

48. D. H. Hanna, G. R. Saad, “Nanocurcumin: preparation, characterization and cytotoxic effects towards human laryngeal cancer cells,” RSC Adv. 10 (2020): 20724-20737. [Google Scholar] [Crossref]

49. G. Guo, S. Z. Fu, L. X. Zhou, H. Liang, M. Fan, F. Luo, Z. Y. Qian, Y. Q. Wei “Preparation of curcumin loaded poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) nanofibers and their in vitro antitumor activity against Glioma 9L cells” Nanoscale 3 (2011): 3825-3832. [Google Scholar] [Crossref]

50. C. Wang, C. Ma, Z. Wu, H. Liang, P. Yan, J. Song, N. Ma, Q. Zhao “Enhanced Bioavailability and Anticancer Effect of Curcumin-Loaded Electrospun Nanofiber: In Vitro and In Vivo Study” Nanoscale Res Lett. 10, no. 1 (2015): 439. [Google Scholar] [Crossref]

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