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IRC-SET 2018 pp 321-333 | Cite as

Buccal Delivery of Curcumin to Address Its Poor Gastrointestinal Stability

  • Bing Lim
  • Mak Wai ThengEmail author
Conference paper

Abstract

Curcumin has numerous health benefits but has low bioavailability in the digestive system due to its low aqueous solubility, high metabolism rate caused by bile (from the liver), and degradation of curcumin under the basic conditions of the small intestine. The alternative way of delivering curcumin into the systemic circulation is through the buccal mucosa, but curcumin has to be delivered quickly before it undergoes degradation under the neutral conditions of the mouth. Oral disintegrating films (ODFs) are investigated as a pathway to release nanoparticles across the buccal mucosa to improve bioavailability. Chitosan, a mucoadhesive polymer, is used to coat nanoparticles. Pregelatinized starch (PGS), granular hydroxypropyl starch (GHS), hydroxypropylmethylcellulose (HPMC) and polyvinyl alcohol (PVA) are mucoadhesive polymers used in films, and propylene glycol (PG) as plasticizer. Mass, thickness, percentage recovery, surface pH, disintegration time and dissolution are assessed for each film. All films have a surface pH of around 6.7, making them non-irritant. Films with formulation of GHS and HPMC has highest maximum percentage dissolution, and has high percentage recovery, giving high drug load. It has released more curcumin than other films in the same time frame, allowing for curcumin to be released quickly. The average disintegration time for it is 53 minutes, which is long for ODFs. More drug can be released across the buccal mucosa over a longer timeframe. Films with PVA may be the thinnest and lightest, but break upon handling, making them hard to apply onto the buccal mucosa and unsuitable as an oral film.

Keywords

Curcumin Oral disintegrating films Nanoparticles Bioavailability 

Notes

Acknowledgements

We thank Associate Professor Kunn Hadinoto Ong, Mr. William Phua, and Lim Li Ming for helping us throughout our project as our supervisor, teacher mentor and student mentor respectively.

References

  1. 1.
    Adahoun, M. A., Al-Akhras, M. H., Jaafar, M. S., & Bououdina, M. (2016). Enhanced anti-cancer and antimicrobial activities of curcumin nanoparticles. Artificial Cells, Nanomedicine, and Biotechnology, 45(1), 98–107.CrossRefGoogle Scholar
  2. 2.
    Maheshwari, R. K., Singh, A. K., Gaddipati, J., & Srimal, R. C. (2006). Multiple biological activities of curcumin: A short review. Life Sciences, 78(18), 2081–2087.CrossRefGoogle Scholar
  3. 3.
    Duvoix, A., Blasius, R., Delhalle, S., Schnekenburger, M., Morceau, F., Henry, E., et al. (2005). Chemopreventive and therapeutic effects of curcumin. Cancer Letters, 223(2), 181–190.CrossRefGoogle Scholar
  4. 4.
    Aggarwal, B. B., Kumar, A., & Bharti, A. C. (2003). Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Research, 23, 363–398.PubMedGoogle Scholar
  5. 5.
    Wang, Z., Zhang, Y., Banerjee, S., Li, Y., & Sarkar, F. H. (2006). 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.CrossRefGoogle Scholar
  6. 6.
    Lev-Ari, S., Zinger, H., Kazanov, D., Yona, D., Ben-Yosef, R., Starr, A., et al. (2005). Curcumin synergistically potentiates the growth inhibitory and pro-apoptotic effects of celecoxib in pancreatic adenocarcinoma cells. Biomedicine and Pharmacotherapy, 59(Suppl 2), S276–280.CrossRefGoogle Scholar
  7. 7.
    Aggarwal, B. B., Shishodia, S., Takada, Y., Banerjee, S., Newman, R. A., Bueso- Ramos, C. E., et al. (2005). Curcumin suppresses the Paclitaxel induced nuclear factor-kappaB pathway in breast cancer cells and inhibits lung metastasis of human breast cancer in nude mice. Clinical Cancer Research, 11, 7490–7498.CrossRefGoogle Scholar
  8. 8.
    Khor, T. O., Keum, Y. S., Lin, W., Kim, J. H., Hu, R., Shen, G., et al. (2006). Combined inhibitory effects of curcumin and phenethyl isothiocyanate on the growth of human PC-3 prostate xenografts in immunodeficient mice. Cancer Research, 66, 613–621.CrossRefGoogle Scholar
  9. 9.
    Bisht, S., Feldmann, G., Soni, S., Ravi, R., Karikar, C., Maitra, A., et al. (2007). Polymeric nanoparticle-encapsulated curcumin (‘nanocurcumin’): A novel strategy for human cancer therapy. Journal of Nanobiotechnology, 5, 3.CrossRefGoogle Scholar
  10. 10.
    Deeb, D., Jiang, H., Gao, X., Hafner, M. S., Wong, H., Divine, G., et al. (2004). Curcumin sensitizes prostate cancer cells to tumor necrosis factor-related apoptosis inducing ligand/Apo2L by inhibiting nuclear factor-kappaB through suppression of IkappaBalpha phosphorylation. Molecular Cancer Therapeutics, 3, 803–812.PubMedGoogle Scholar
  11. 11.
    Lev-Ari, S., Strier, L., Kazanov, D., Madar-Shapiro, L., Dvory-Sobol, H., Pinchuk, I., et al. (2005). Celecoxib and curcumin synergistically inhibit the growth of colorectal cancer cells. Clinical Cancer Research, 11, 6738–6744.CrossRefGoogle Scholar
  12. 12.
    Mahmood, K., Zia, K. M., Zuber, M., Nazli, Z., Rehman, S., & Zia, F. (2016). Enhancement of bioactivity and bioavailability of curcumin with chitosan based materials. Korean Journal of Chemical Engineering, 33(12), 3316–3329.CrossRefGoogle Scholar
  13. 13.
    Liu, W., Zhai, Y., Heng, X., Che, F. Y., Chen, W., Sun, D., et al. (2016). Oral bioavailability of curcumin: Problems and advancements. Journal of Drug Targeting, 4(8), 694–702.CrossRefGoogle Scholar
  14. 14.
    Rajalakshmi, R., Indira, Y., Aruna, U., Vinesha, V., Rupangada, V., & Krishna, S. B. (2014). Chitosan nanoparticles—An emerging trend in nanotechnology. International Journal of Drug Delivery, 6(3), 204–229.Google Scholar
  15. 15.
    Rajan, S. S., Pandian, A., & Palaniappan, T. (2016). Curcumin loaded in bovine serum albumin–chitosan derived nanoparticles for targeted drug delivery. Bulletin of Materials Science, 39(3), 811–817.CrossRefGoogle Scholar
  16. 16.
    Aggarwal, B. B., Kumar, A., & Bharti, A. C. (2003). Anticancer potential of curcumin: Preclinical and clinical studies. Anticancer Research, 23(1A), 363–398.PubMedGoogle Scholar
  17. 17.
    Hanif, M., & Zaman, M. (2017). Thiolation of arabinoxylan and its application in the fabrication of controlled release mucoadhesive oral films. DARU Journal of Pharmaceutical Sciences, 25(1), 6.CrossRefGoogle Scholar
  18. 18.
    Patel, R., & Shah, D. (2015). Nanoparticles loaded sublingual film as an effective treatment of chemotherapy induced nausea and vomiting. International Journal of PharmTech Research, 8(10), 77–87.Google Scholar
  19. 19.
    Mazzarino, L., Borsali, R., & Lemos-Senna, E. (2014). Mucoadhesive films containing chitosan-coated nanoparticles: A new strategy for buccal curcumin release. Journal of Pharmaceutical Sciences, 103(11), 3764–3771.  https://doi.org/10.1002/jps.24142.CrossRefPubMedGoogle Scholar
  20. 20.
    Mašek, J., Lubasová, D., Lukáč, R., Turánek-Knotigová, P., Kulich, P., Plocková, J., et al. (2017). Multi-layered nanofibrous mucoadhesive films for buccal and sublingual administration of drug-delivery and vaccination nanoparticles - important step towards effective mucosal vaccines. Journal of Controlled Release, 249, 183–195.CrossRefGoogle Scholar
  21. 21.
    Laffleur, F., Schmelzle, F., Ganner, A., & Vanicek, S. (2016). In vitro and ex vivo evaluation of novel curcumin-loaded excipient for Buccal delivery. AAPS PharmSciTech.Google Scholar
  22. 22.
    Mazzarino, L., Coche-Guérente, L., Lemos-Senna, P. L., & Borsali, R. (2014). On the mucoadhesive properties of chitosan-coated polycaprolactone nanoparticles loaded with curcumin using quartz crystal microbalance with dissipation monitoring. Journal of Biomedical Nanotechnology, 10(5), 787–794.CrossRefGoogle Scholar
  23. 23.
    Mazzarino, L., Travelet, C., Ortega-Murillo, S., Otsuka, I., Pignot-Paintrand, I., Lemos-Senna, E., et al. (2012). Elaboration of chitosan-coated nanoparticles loaded with curcumin for mucoadhesive applications. Journal of Colloid and Interface Science, 370(1), 58–66.CrossRefGoogle Scholar
  24. 24.
    Ramdayal, G., Suresh, P., & Kr, S. U. (2011). Comparative study on novel pregelatinized garadu starch PGGS and starch 1500 as a direct compression/wet-granulation tableting excipient. Journal of Pharmacy Research, 4, 2406–2410.Google Scholar
  25. 25.
    Muppalaneni, S., & Omidian, H. (2013). Polyvinyl alcohol in medicine and pharmacy: A perspective. Journal of Developing Drugs, 02(03).  https://doi.org/10.4172/2329-6631.1000112.
  26. 26.
    Karki, S., Kim, H., Na, S., Shin, D., Jo, K., & Lee, J. (2016). Thin films as an emerging platform for drug delivery. Asian Journal of Pharmaceutical Sciences, 11(5), 559–574. Retrieved from  https://doi.org/10.1016/j.ajps.2016.05.004.
  27. 27.
    Muralisrinivasan, N. S. (2017). Polymer blends and composites: Chemistry and technology. Hoboken, NJ: John Wiley & Sons Inc.Google Scholar
  28. 28.
    Okaya, T., Kohno, H., Terada, K., Sato, T., Maruyama, H., & Yamauchi, J. (1992). Specific interaction of starch and polyvinyl alcohols having long alkyl groups. Journal of Applied Polymer Science, 45(7), 1127–1134.  https://doi.org/10.1002/app.1992.070450701.CrossRefGoogle Scholar
  29. 29.
    Rane, S. S., Hamed, E., & Rieschl, S. (2012). An exact model for predicting tablet and blend content uniformity based on the theory of fluctuations in mixtures. Journal of Pharmaceutical Sciences, 101(12), 4501–4515.  https://doi.org/10.1002/jps.23313.CrossRefPubMedGoogle Scholar
  30. 30.
    Choi, D., & Hong, J. (2013). Layer-by-layer assembly of multilayer films for controlled drug release. Archives of Pharmacal Research, 37(1), 79–87.  https://doi.org/10.1007/s12272-013-0289-x.CrossRefPubMedGoogle Scholar
  31. 31.
    Lindert, S., & Breitkreutz, J. (2017). Oromucosal multilayer films for tailor-made, controlled drug delivery. Expert Opinion on Drug Delivery, 1–15.  https://doi.org/10.1080/17425247.2017.1276899.
  32. 32.
    Choi, M., Kim, K., Heo, J., Jeong, H., Kim, S. Y., & Hong, J. (2015). Multilayered graphene nano-film for controlled protein delivery by desired electro-stimuli. Scientific Reports, 5(1).  https://doi.org/10.1038/srep17631.

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.National Junior CollegeSingaporeSingapore

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