Nanoparticles containing curcuminoids (Curcuma longa): development of topical delivery formulation

Abstract

Solid lipid nanoparticles incorporating Curcuma longa L., Zingiberaceae, curcuminoids were produced by the hot melt emulsion method. A Box-Behnken factorial design was adopted to study the nanoparticles production at different levels of factors such as the percentage of curcuminoids, time of homogeniza-tion and surfactant ratio. The optimized nanoparticles were incorporated into hydrogels for stability, drug release and skin permeation tests. The average nanoparticle sizes were 210.4nm; the zeta poten-tial of -30.40 ±4.16; the polydispersivity was 0.222 ±0.125. The average encapsulation efficiency of curcumin and curcuminoids was 52.92 ± 5.41% and 48.39 ± 6.62%, respectively. Solid lipid nanocapsules were obtained with curcumin load varying from 14.2 to 33.6% and total curcuminoids load as high as 47.7%. The topical formulation containing SLN-Curcuminoids showed good spreadability and stability when subjected to mechanical stress test remained with characteristic color, showed no phase separa-tion and no significant change in pH. As a result of slow release, the nanoparticles were able to avoid permeation or penetration in the pig ear epidermis/dermis during 18h. The topical formulation is sta-ble and can be used in further in vivo studies for the treatment of inflammatory reactions, in special for radiodermitis.

References

  1. Aggarwal, B., Harikumar, K.B., 2009. Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int. J. Biochem. Cell Biol. 1, 40–59.

    Google Scholar 

  2. Anvisa, 2004. Guia de Estabilidade de Produtos Cosméticos. In: Ministério da Saúde. Agência Nacional de Vigilância Sanitária, 1st ed. Anvisa, Brasília (Série Qualidade em Cosméticos, 1).

    Google Scholar 

  3. Attama, A.A., Muller-Goymann, C.C., 2008. Effects of beeswax modifications on the lipid matrix of solid lipid nanoparticles crystallinity. Colloids Surf. A 315, 189–195.

    CAS  Google Scholar 

  4. Augustyniak, A., Bartosz, G., Cipak, A., Duburs, G., Kov L’Ubica, H., Luczaj, W., Majekova, M., Odysseos, A.D., Rackova, L., Skrzydlewska, E., Stefek, M., Strosov, M., Tirzitis, G., Venskutonis, P.R., Viskupicova, J., Vraka, P.S., Zarkovi, N., 2010. Natural and synthetic antioxidants: an updated overview. Free Radic. Res. 44, 1216–1262.

    CAS  PubMed  Google Scholar 

  5. Bisht, S., Feldmann, G., Soni, S., Ravi, R., Karikar, C., Maitra, A., Maitral, A., 2007. Polymeric nanoparticle-encapsulated curcumin (“nanocurcumin”): a novel strategy for human cancer therapy. J. Nanobiotechnol., https://doi.org/10.1186/1477-3155-5-3.

    Google Scholar 

  6. Box, G.E.P., Hunter, W.G., Hunter, J.S., 1978. Statistics for Experimenters. John Wiley & Sons, New York.

    Google Scholar 

  7. Cevc, G., Vieri, U., 2010. Nanotechnology and the transdermal route. A state of the art review and critical appraisal. J. Control. Release 141, 277–299.

    CAS  PubMed  Google Scholar 

  8. Contri, R.V., Fiel, L.A., Pohlmann, A.R., Guterres, S.S., Beck, R.C.R., 2011. Transport of substances and nanoparticles across the skin and in vitro models to evaluate skin permeation and/or penetration. In: Beck, R.C.R., Guterres, S.S., Pohlmann, A.R. (Eds.), Nanocosmetics and Nanomedicine., pp. 3–35.

    Google Scholar 

  9. Das, R.K., Kasoju, N., Bora, U., 2010. Encapsulation of curcumin in alginate-chitosan-pluronic composite nanoparticles for delivery to cancer cells. Nanomed. Nanotechnol. 6, 153–160.

    CAS  Google Scholar 

  10. Farmacopeia Brasileira, 2010. Ministério da Saúde. Agência Nacional de Vigilância Sanitária, Brasília http://www.anvisa.gov.br/hotsite/cd_farmacopeia/ pdf/volume1%2020110216.pdf (accessed September 2011).

    Google Scholar 

  11. Gao, Y., Li, Z., Sun, M., Guo, C., Yu, A., Xi, Y., Cui, J., Lou, H., Zhai, G., 2011. Preparation and characterization of intravenously injectable curcumin nanosuspension. Drug Deliv. 18, 131–142.

    CAS  PubMed  Google Scholar 

  12. Goel, A., Kunnumakkara, A.B., Aggarwal, B.B., 2008. Curcumin as “Curecumin”: from kitchen to clinic. Biochem. Pharmacol. 75, 787–809.

    CAS  PubMed  Google Scholar 

  13. Guterres, S.S., Alves, M.P., Pohlmann, A.R., 2007. Polymeric nanoparticles, nanospheres and nanocapsules forcutaneous applications. Drug Target Insights 2, 147–157.

    PubMed  PubMed Central  Google Scholar 

  14. Irving, G.R., Karmokar, A., Berry, D.P., Brown, K., Steward, W.P., 2011. Curcumin: the potential for efficacy in gastrointestinal diseases. Best Pract. Res. Clin. Gastroenterol. 25, 519–534.

    CAS  PubMed  Google Scholar 

  15. Jayaprakasha, G.K., Rao, L.J., Sakariah, K.K., 2006. Antioxidant activities of curcumin, demethoxycurcumin and bisdemethoxycurcumin. Food Chem. 98, 720–724.

    CAS  Google Scholar 

  16. Jebors, S., Leydier, A., Wu, Q., Ghera, B.B., Malbouyre, M., Coleman, A.W., 2010. Solid lipid nanoparticles (SLNs) derived from para-acyl-calix[9]-arene: preparation and stability. J. Microencapsul. 27, 561–571.

    CAS  PubMed  Google Scholar 

  17. Jenning, V., Gysler, A., Schafer-Korting, M., Gohla, S.H., 2000. Vitamin A loaded solid lipid nanoparticles for topical use: occlusive properties and drug targeting to the upper skin. Eur. J. Pharm. Biopharm. 49, 211–218.

    CAS  PubMed  Google Scholar 

  18. Küchler, S., Abdel-Mottaleb, M., Lamprecht, A., Radowski, M.R., Haag, R., Schäfer-Korting, M., 2009. Influence of nanocarrier type and size on skin delivery of hydrophilic agents. Int. J. Pharm. 377, 169–172.

    PubMed  Google Scholar 

  19. Luengo, J., Weiss, B., Schneider, M., Ehlers, A., Stracke, F., König, K., Kostka, K.H., Lehr, C.M., Schaefer, U.F., 2006. Influence of nanoencapsulation on human skin transport of flufenamic acid. Skin Pharmacol. Appl. Skin Physiol. 19, 190–197.

    CAS  Google Scholar 

  20. Lyra, M.A.M., Soares-Sobrinho, J.L., Brasileiro, M.T., Roca, M.F.L., Barraza, J.A., Viana, O.S., Rolim-Neto, P.J., 2007. Sistemas matriciais hidrofílicos e mucoadesivos para liberac¸ão controlada de fármacos Lat. Am. J. Pharm. 26, 784–793.

    Google Scholar 

  21. Martin, A.N., 1993. Physical Pharmacy: Physical Chemical Principles in the Pharma-ceutical Sciences, 2nd ed. Lippincott Williams & Wilkins, Philadelphia, PA, USA, pp. 622.

    Google Scholar 

  22. Martins, M.R.F.M., Veiga, F., 2002. Promotores de permeac¸ão para a liberac¸ão trans-dérmica de fármacos: uma nova aplicac¸ão para as ciclodextrinas. Rev. Bras. Farmacol. 38, 33–54.

    CAS  Google Scholar 

  23. Martins, R.M., 2014. Influência de micro e nanopartículas lipídicas sólidas na eficiência de formulac¸ões fotoprotetoras bioativas. Tese de Doutorado, Faculdade de Ciências Farmacêuticas de Ribeirão Preto da Universidade de São Paulo, Ribeirão Preto, pp. 181.

    Google Scholar 

  24. Mehnert, W., Mader, K., 2001. Solid lipid nanoparticles: production, characterization and applications. Adv. Drug Deliv. Rev. 47, 165–196.

    CAS  PubMed  Google Scholar 

  25. Mourtas, S., Canovi, M., Zona, C., Aurilia, D., Niarakis, A., La Ferla, B., Salmona, M., Nicotra, F., Gobbi, M., Antimisiaris, S.G., 2011. Curcumin-decorated nanoliposomes with very high affinity for amyloid-FJ 1-42 peptide. Biomaterials 32, 1635–1645.

    CAS  PubMed  Google Scholar 

  26. Nair, H.B., Sung, B., Yadav, V.R., Kannappan, R., Chaturvedi, M.M., Aggarwal, B.B., 2010. Delivery of antiinflammatory nutraceuticals by nanoparticles forthe pre-vention and treatment of cancer. Biochem. Pharmacol. 80, 1833–1843.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Nayak, A.P., Tiyaboonchai, W., Patankar, S., Madhusudhan, B., Souto, E.B., 2010. Curcuminoida-loaded lipid nanoparticles: novel approach towards malaria treatment. Colloid Surf. B 81, 263–273.

    CAS  Google Scholar 

  28. Oliveira, R.C.S., 2008. Desenvolvimento, formulac¸ão e avaliac¸ão de sistemas de libertac¸ão transdérmica incorporando sistemas ternários de complexac¸ão (Tese de Doutorado). Universidade do Porto, Portugal.

    Google Scholar 

  29. Paulucci, V.P., Couto, R.O., Teixeira, C.C.C., Freitas, L.A.P., 2013. Optimization of the extraction of curcumin from Curcuma longa rhizomes. Rev. Bras. Farmacogn. 23, 94–100.

    CAS  Google Scholar 

  30. Puglia, C., Frasca, G., Musumeci, T., Rizza, L., Puglisi, G., Bonina, F., Chiechio, S., 2012. Curcumin loaded NLC induces histone hypoacetylation in the CNS after intraperitoneal administration in mice. Eur.J. Pharm. Biopharm. 81, 288–293.

    CAS  PubMed  Google Scholar 

  31. Rusig, O., Martins, M.C., 1992. Efeito da temperatura, do pH e da luz sobre extratos de oleorresina de cúrcuma (Curcuma longa L.) e curcumina. Rev. Bras. Cor. Nat. 1, 158–164.

    Google Scholar 

  32. Sartorelli, P., Anderson, H.R., Angerer, J., Corish, J., Drexler, H., Goen, T., 2000. Percu-taneous penetration studies for risk assessment. Environ. Toxicol. Pharmacol. 8, 133–152.

    CAS  PubMed  Google Scholar 

  33. Serra, M.L.G., Vásquez, M.L.R., Villafuerte, L.R., Garcia, B.F., Hernandez, A.L., 2009. Efecto de los componentes de la formulación en las propiedades de las nanopartículas lipídicas sólidas. Rev. Mex. Cienc. Farm. 40, 26–40.

    Google Scholar 

  34. Suwantong, O., Waleetorncheepsawat, S., Sanchavanakit, N., Pavasant, P., Cheepsunthorn, P., Bunaprasert, T., Supaphol, P., 2007. In vitro biocompatibility of electrospun poly(3-hydroxybutyrate) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) fiber mats. Int. J. Biol. Macromol. 40, 217–223.

    CAS  PubMed  Google Scholar 

  35. Tønnesen, H.H., Karlsen, J., 1985. Studies on curcumin and curcuminoids: VIkinet-ics of curcumin degradation in aqueous solution. Z. Lebensm. Unters. For. 180, 402–404.

    Google Scholar 

  36. Yallapu, M.M., Jaggi, M., Chauhan, S.C., 2012. Curcumin nanoformulations: a future nanomedicine for cancer. Drug Discov. Today 17, 71–80.

    CAS  PubMed  Google Scholar 

  37. Yallapu, M.M., Jaggi, M., Chauhan, S.C., 2013. Curcumin nanomedicine: a road to cancer therapeutics. Curr. Pharm. Design 19, 1994–2010.

    CAS  Google Scholar 

  38. Wissing, S.A., Lippacher, A., Muller, R.H., 2001. Investigations onthe occlusive properties of solid lipid nanoparticles (SLN). J. Cosmet. Sci. 52, 313–324.

    CAS  PubMed  Google Scholar 

  39. Zamarioli, C.M., 2014. Formulac¸ão tópica para prevenc¸ão e tratamento de radio-dermites: desenvolvimento de nanopartículas lipídicas sólidas (NLS) contendo curcuminoidese estudo invitro. Dissertac¸ão de Mestrado, Escola de Enfermagem de Ribeirão Preto da Universidade de São Paulo, Ribeirão Preto, pp. 139.

    Google Scholar 

  40. Zetasizer Nano-ZS, 2009. User Instructions. NBTC User Instructions.

    Google Scholar 

  41. Zhou, H., Beevers, C.S., Huang, S., 2011. The targets of curcumin. Curr. DrugTargets 12, 332–347.

    CAS  Google Scholar 

Download references

Acknowledgments

Authors acknowledge the financial support from CAPES (MSc Scholarship), Fapesp (2011/20872-7) and CNPq (PQ-2).

Author information

Affiliations

Authors

Contributions

CMZ (MSc student) was responsible for most of experimental work (nanocapsules, gel and characterization); RMM developed the nanoencapsulation technique and contributed in all laboratory work and chromatographic analysis. ECC idealized the work and contributed to critical reading of the manuscript. LAPF designed the study, supervised the experiments, critically read and defined the final version of the manuscript. All the authors have read the final manuscript and approved the submission.

Corresponding author

Correspondence to Luis A. P. Freitas.

Ethics declarations

The authors declare no conflicts of interest.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zamarioli, C.M., Martins, R.M., Carvalho, E.C. et al. Nanoparticles containing curcuminoids (Curcuma longa): development of topical delivery formulation. Rev. Bras. Farmacogn. 25, 53–60 (2015). https://doi.org/10.1016/j.bjp.2014.11.010

Download citation

Keywords

  • Solid lipid nanoparticles
  • Beeswax
  • Pig skin
  • Curcumin