Buccal Delivery of Curcumin to Address Its Poor Gastrointestinal Stability
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.
KeywordsCurcumin Oral disintegrating films Nanoparticles Bioavailability
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.
- 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.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
- 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
- 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
- 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
- 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.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.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
- 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.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.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.Muralisrinivasan, N. S. (2017). Polymer blends and composites: Chemistry and technology. Hoboken, NJ: John Wiley & Sons Inc.Google Scholar
- 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.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.