Applied Chemistry for Engineering (공업화학)

The Korean Society of Industrial and Engineering Chemistry (한국공업화학회)
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Preparation of Curcumin-loaded Dequalinium Emulsion for Mitochondria-targeted Drug Delivery

미토콘드리아 표적 약물 전달을 위한 curcumin 함유 dequalinium emulsion 제조

  • Hye Won Park (Department of Biochemistry, Chungnam National University) ;
  • Joon Sig Choi (Department of Biochemistry, Chungnam National University)
  • Received : 2024.08.01
  • Accepted : 2024.08.29
  • Published : 2024.10.10
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Abstract

This study focused on the development of a dequalinium-containing oil-in-water (O/W) emulsion (DQE) system for delivering the mitochondria-targeted anticancer agent, curcumin. Dequalinium is a mitochondria-targeting agent with known antibacterial and anticancer properties, and its efficacy in treating malaria has been previously recognized. Structurally, dequalinium is amphiphilic, comprising hydrophobic methylene and hydrophilic quinaldinium groups. In this study, curcumin, a well-documented anticancer and antioxidant compound, was incorporated into the oil phase of an emulsion using dequalinium as the emulsifier. Castor oil, chosen for its biodegradability and high stability in the body, was used as the oil phase in this study. The curcumin-loaded DQE was prepared using ultrasonic sonication followed by homogenization. The morphology and size distribution of the emulsion particles, as assessed using nanoparticle analysis, atomic force microscopy, and transmission electron microscopy, ranged from 100-200 nm. Confocal microscopy confirmed the efficient mitochondrial targeting ability of DQE in HeLa cells. These findings establish the DQE system as a promising drug delivery platform with efficient mitochondrial targeting capabilities and the potential to encapsulate water-insoluble drugs.

Keywords

Acknowledgement

This work was supported by the Research Fund of the Chungnam National University.

References

  1. M. Dhaval, P. Vaghela, K. Patel, K. Sojitra, M. Patel, S. Patel, K. Dudhat, S. Shah, R. Manek, and R. Parmar, Lipid-based emulsion drug delivery systems - A comprehensive review, Drug Deliv. Transl. Res., 12, 1616-1639 (2022). https://doi.org/10.1007/s13346-021-01071-9
  2. M. Mehta, T. A. Bui, X. Yang, Y. Aksoy, E. M. Goldys, and Wei Deng, Lipid-based nanoparticles for drug/gene delivery: An overview of the production techniques and difficulties encountered in their industrial development, ACS Mater. Au, 3, 600-619 (2023). https://doi.org/10.1021/acsmaterialsau.3c00032
  3. H. H. Tayeb, R. Felimban, S. Almaghrabi, and N. Hasaballah, Nanoemulsions: Formulation, characterization, biological fate, and potential role against COVID-19 and other viral outbreaks, Colloid Interface Sci. Commun., 45, 100533 (2021).
  4. J. Wadhwa, A. Nair, and R. Kumria, Emulsion forming drug delivery system for lipophilic drugs, Acta Pol. Pharm., 69, 179-191 (2012).
  5. R. J. Wilson, Y. Li, G Yang, and C. X. Zhao, Nanoemulsions for drug delivery, Particuology, 64, 85-97 (2022). https://doi.org/10.1016/j.partic.2021.05.009
  6. S. Tamilvanan, Oil-in-water lipid emulsions: Implications for parenteral and ocular delivering systems, Prog. Lipid Res., 43, 489-533 (2004). https://doi.org/10.1016/j.plipres.2004.09.001
  7. S. B. Tiwari and M. M. Amiji, Improved oral delivery of paclitaxel following administration in nanoemulsion formulations, J. Nanosci. Nanotechnol., 6, 3215-3221 (2006). https://doi.org/10.1166/jnn.2006.440
  8. A. T. Florence and J. A. Rogers, Emulsion stabilization by non-ionic surfactants: Experiment and theory, J. Pharm. Pharmacol., 23, 153-169 (1971). https://doi.org/10.1111/j.2042-7158.1971.tb08637.x
  9. D. J. McClements and S. M. Jafari, Nanoemulsions: Formulation, Applications, and Characterization, 1st ed., 3-20, Academic press, Cambridge, USA (2018).
  10. B. W. Barry, The control of oil-in-water emulsion consistency using mixed emulsifiers, J. Pharm. Pharmacol., 21, 533-540 (1969). https://doi.org/10.1111/j.2042-7158.1969.tb08307.x
  11. V. Weissig, C. Lizano, and V. P. Torchilin, Selective DNA release from DQAsome/DNA complexes at mitochondria-like membranes, Drug Deliv., 7, 1-5 (2002).
  12. V. Weissig, G. G. D'Souza, and V.P. Torchilin, DQAsome/DNA complexes release DNA upon contact with isolated mouse liver mitochondria, J. Control. Release., 75, 401-408 (2001). https://doi.org/10.1016/S0168-3659(01)00392-3
  13. G. G. D'Souza, R. Rammohan, S. M. Cheng, V. P. Torchilin, and V. Weissig, DQAsome-mediated delivery of plasmid DNA toward mitochondria in living cells, J. Control. Release., 92, 189-197 (2003). https://doi.org/10.1016/S0168-3659(03)00297-9
  14. S. Zupancic, P. Kocbek, M. G. Zariwala, D. Renshaw, M. O. Gul, Z. Elsaid, K. M. Taylor, and S. Somavarapu, Design and development of novel mitochondrial targeted nanocarriers, DQAsomes for curcumin inhalation, Mol. Pharm., 11, 2334-2345 (2014). https://doi.org/10.1021/mp500003q
  15. H. D. Dell and R. Kamp, Determination of dequalinium compounds in biological material, Arch. Pharm., 305, 368-373 (1972). https://doi.org/10.1002/ardp.19723050510
  16. M. J. Weiss, J. R. Wong, C. S. Ha, R. Bleday, R. R. Salem, G. D. Steele Jr, and L. B. Chen, Dequalinium, a topical antimicrobial agent, displays anticarcinoma activity based on selective mitochontrial accumulation, Proc. Natl. Acad. Sci. U.S.A., 84, 5444-5448 (1987). https://doi.org/10.1073/pnas.84.15.5444
  17. M. Alaayedi, H. Mahmood, and A. Saeed, The enhancement effect of castor oil on the permeability of flurbiprofen as transdermal gel, Int. J. App. Pharm., 10, 140-144 (2018). https://doi.org/10.22159/ijap.2018v10i1.23348
  18. H. Rachmawati, Y. A. Arvin, S. Asyarie, K. Anggadiredja, R. R. Tjandrawinata, and G. Storm, Local sustained delivery of bupivacaine HCl from a new castor oil-based nanoemulsion system, Drug Deliv. Transl. Res., 8, 515-524 (2018).
  19. B. B. Aggarwal, A. Kumar, and A. C. Bharti, Anticancer potential of curcumin: preclinical and clinical studies, Anticancer Res., 23, 363-398 (2003).