Abstract
Purpose
Curcumin (CUR), a natural polyphenolic compound, has several pharmacological uses, primarily regarding its anti-inflammatory, chemotherapeutic, and antioxidant properties. However, to date, a significant drawback of curcumin is its poor bioavailability due to its low solubility and permeability. Therefore, the association of curcumin in polymeric nanocapsules may be an excellent strategy to increase its bioavailability.
Methods
Two nanocapsule systems were developed with an oily core of vitamin E surrounded by a biodegradable polymeric shell of either chitosan (NC-CS) or alginate (NC-ALG) capable of improving the encapsulation efficiency, stability, and permeability of CUR. NC-CS and NC-ALG showed particle sizes of approximately 116.7 ± 3.2 and 178 ± 7.9 nm, dispersities of 0.107 and 0.149, and zeta potentials of 24.4 ± 2.1 and − 49.0 ± 2.3 mV, respectively.
Results
The encapsulation efficiency was approximately 90% in both cases, and they were demonstrated to be stable under storage conditions for 3 months. Cytotoxicity studies performed in Caco-2 cells using the method of trypan blue dye revealed that even at a high concentration of chitosan and alginate (157.9 μg/cm2 or 600 mg/mL), both of the nanocapsules were not toxic, exhibiting cell viability > 80%. The permeability was evaluated using Caco-2 cells as an in vitro model of the epithelial barrier. The obtained results show that the permeability of NC-CS and NC-ALG encapsulated CUR was considerably higher compared to that of an aqueous suspension.
Conclusions
The obtained results suggest that nanocapsules could improve the solubility, permeability, and stability of curcumin.
Similar content being viewed by others
References
Ak T, Gülçin İ. Antioxidant and radical scavenging properties of curcumin. Chem Biol Interact. 2008;174:27–37. Available from: http://www.sciencedirect.com/science/article/pii/S0009279708002573
Priyadarsini IK. The chemistry of curcumin: from extraction to therapeutic agent. Molecules. 2014;19:20091–112.
Began G, Sudharshan E, Appu Rao AG. Inhibition of lipoxygenase one by phosphatidylcholine micelles-bound curcumin. Lipids Germany. 1998;33:1223–8.
Chan MM-Y, Huang H-I, Fenton MR, Fong D. In vivo inhibition of nitric oxide synthase gene expression by curcumin, a cancer preventive natural product with anti-inflammatory properties. Biochem Pharmacol. 1998;55:1955–62. Available from: http://www.sciencedirect.com/science/article/pii/S0006295298001142
Menon VP, Sudheer AR. In: Aggarwal BB, Surh Y-J, Shishodia S, editors. Antioxidant and anti-inflammatory properties of curcumin—the molecular targets and therapeutic uses of curcumin in health and disease. Boston: Springer US; 2007. p. 105–25. Available from: https://doi.org/10.1007/978-0-387-46401-5_3.
Wongcharoen W, Phrommintikul A. The protective role of curcumin in cardiovascular diseases. Int J Cardiol. 2009;133:145–51. Available from: http://www.sciencedirect.com/science/article/pii/S0167527309001132
Hamaguchi T, Ono K, Yamada M. REVIEW: curcumin and Alzheimer’s disease. CNS Neurosci Ther England. 2010;16:285–97.
Mythri RB, Bharath MMS. Curcumin: a potential neuroprotective agent in Parkinson’s disease. Curr Pharm Des Netherlands. 2012;18:91–9.
Maradana MR, Thomas R, O’Sullivan BJ. Targeted delivery of curcumin for treating type 2 diabetes. Mol Nutr Food Res Germany. 2013;57:1550–6.
Sahebkar A. Dual effect of curcumin in preventing atherosclerosis: the potential role of pro-oxidant–antioxidant mechanisms. Nat Prod Res [Internet]. Taylor & Francis; 2015;29:491–2. Available from: https://doi.org/10.1080/14786419.2014.956212.
Wanninger S, Lorenz V, Subhan A, Edelmann FT. Metal complexes of curcumin—synthetic strategies, structures, and medicinal applications. Chem Soc Rev [Internet]. The Royal Society of Chemistry; 2015;44:4986–5002. Available from: https://doi.org/10.1039/C5CS00088B
López-Lázaro M. Anticancer and carcinogenic properties of curcumin: considerations for its clinical development as a cancer chemopreventive and chemotherapeutic agent. Mol Nutr Food Res. Wiley Online Library; 2008;52.
Tuorkey M. Curcumin a potent cancer preventive agent: mechanisms of cancer cell killing. Interv Med Appl Sci Akadémiai Kiadó. 2014;6:139–46.
Mazzarino L, Dora CL, Bellettini IC, Minatti E, Cardoso SG, Lemos-Senna E. Curcumin-loaded polymeric and lipid nanocapsules: preparation, characterization and chemical stability evaluation. Lat Am J Pharm. 2010;29:933–40.
Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm ACS Publications. 2007;4:807–18.
Lin C-C, Lin H-Y, Chen H-C, Yu M-W, Lee M-H. Stability and characterization of phospholipid-based curcumin-encapsulated microemulsions. Food Chem Elsevier. 2009;116:923–8.
Ahmed TA, Aljaeid BM. Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery. Drug Des Devel Ther. Dove Press; 2016;10:483.
Agnihotri SA, Mallikarjuna NN, Aminabhavi TM. Recent advances on chitosan-based micro-and nanoparticles in drug delivery. J Control Release Elsevier. 2004;100:5–28.
Szymańska E, Winnicka K. Stability of chitosan—a challenge for pharmaceutical and biomedical applications. Mar Drugs Multidiscip Digital Publish Inst. 2015;13:1819–46.
Lertsutthiwong P, Noomun K, Jongaroonngamsang N, Rojsitthisak P, Nimmannit U. Preparation of alginate nanocapsules containing turmeric oil. Carbohydr Polym. 2008;74:209–14. Available from: http://www.sciencedirect.com/science/article/pii/S0144861708000817
Natrajan D, Srinivasan S, Sundar K, Ravindran A. Formulation of essential oil-loaded chitosan-alginate nanocapsules. J food drug Anal Elsevier. 2015;23:560–8.
Suhaimi SH, Roslic NA. Effects of formulation parameters on particle size and polydispersity index of Orthosiphon stamineus loaded nanostructured lipid carrier. J Adv Res Appl Sci Eng Technol. 2015;1:36–9.
Khayata N, Abdelwahed W, Chehna MF, Charcosset C, Fessi H. Preparation of vitamin E loaded nanocapsules by the nanoprecipitation method: from laboratory scale to large scale using a membrane contactor. Int J Pharm. 2012;423:419–27. Available from: http://www.sciencedirect.com/science/article/pii/S0378517311011422
Fresta M, Cavallaro G, Giammona G, Wehrli E, Puglisi G. Preparation and characterization of polyethyl-2-cyanoacrylate nanocapsules containing antiepileptic drugs. Biomaterials. 1996;17:751–8. Available from: http://www.sciencedirect.com/science/article/pii/0142961296814116
Vårum KM, Smidsrød O. Structure-property relationship in chitosans. In: Polysaccharides: structural diversity functional versatility. New York: Marcel Dekker; 2005. p. 625–42.
Rokhati N, Widjajanti P, Pramudono B, Susanto H. Performance comparison of α - and β-amylases on chitosan hydrolysis. ISRN Chem Eng. 2013;2013:186159.
Danhier F, Lecouturier N, Vroman B, Jerome C, Marchand-Brynaert J, Feron O, et al. Paclitaxel-loaded PEGylated PLGA-based nanoparticles: in vitro and in vivo evaluation. J Control Release Netherlands. 2009;133:11–7.
Thipparaboina R, Chavan RB, Shastri NR. Nanocrystals for delivery of therapeutic agents. Part Technol Deliv Ther. Springer; 2017. p. 291–316.
Maruyama CR, Guilger M, Pascoli M, Bileshy-José N, Abhilash PC, Fraceto LF, et al. Nanoparticles based on chitosan as carriers for the combined herbicides imazapic and imazapyr. Sci Rep. Nat Publ Group. 2016;6:19768.
Guarino V, Caputo T, Altobelli R, Ambrosio L. Degradation properties and metabolic activity of alginate and chitosan polyelectrolytes for drug delivery and tissue engineering applications. Aims Press; 2015;
Marković D, Zarubica A, Stojković N, Vasić M, Cakić M, Nikolić G. Alginates and similar exopolysaccharides in biomedical application and pharmacy: controlled delivery of drugs. Adv Technol. 2016;5:39–52.
Fröhlich E, Roblegg E. Models for oral uptake of nanoparticles in consumer products. Toxicology Elsevier. 2012;291:10–7.
Ma H, Qi X, Maitani Y, Nagai T. Preparation and characterization of superparamagnetic iron oxide nanoparticles stabilized by alginate. Int J Pharm [Internet]. 2007;333:177–86. Available from: http://www.sciencedirect.com/science/article/pii/S0378517306008131
Huang M, Khor E, Lim L-Y. Uptake and cytotoxicity of chitosan molecules and nanoparticles: effects of molecular weight and degree of deacetylation. Pharm Res United States. 2004;21:344–53.
Schipper NG, Varum KM, Artursson P. Chitosans as absorption enhancers for poorly absorbable drugs. 1: influence of molecular weight and degree of acetylation on drug transport across human intestinal epithelial (Caco-2) cells. Pharm Res United States. 1996;13:1686–92.
Prego C, Fabre M, Torres D, Alonso MJ. Efficacy and mechanism of action of chitosan nanocapsules for oral peptide delivery. Pharm Res. United States. 2006;23:549–56.
Fischer D, Li Y, Ahlemeyer B, Krieglstein J, Kissel T. In vitro cytotoxicity testing of polycations: influence of polymer structure on cell viability and hemolysis. Biomaterials Netherlands. 2003;24:1121–31.
Pasternak AS, Miller WM. Measurement of trans-epithelial electrical resistance in perfusion: potential application for in vitro ocular toxicity testing. Biotechnol Bioeng United States. 1996;50:568–79.
Van der Lubben IM, Verhoef JC, Borchard G, Junginger HE. Chitosan and its derivatives in mucosal drug and vaccine delivery. Eur J Pharm Sci [Internet]. 2001;14:201–7. Available from: http://www.sciencedirect.com/science/article/pii/S0928098701001725
Amidi M, Mastrobattista E, Jiskoot W, Hennink WE. Chitosan-based delivery systems for protein therapeutics and antigens. Adv Drug Deliv Rev Netherlands. 2010;62:59–82.
Xiang Y, Liu Y, Mi B, Leng Y. Hydrated polyamide membrane and its interaction with alginate: a molecular dynamics study. Langmuir United States. 2013;29:11600–8.
Nafee N, Schneider M, Schaefer UF, Lehr C-M. Relevance of the colloidal stability of chitosan/PLGA nanoparticles on their cytotoxicity profile. Int J Pharm Netherlands. 2009;381:130–9.
Rodrigues S, Dionisio M, Lopez CR, Grenha A. Biocompatibility of chitosan carriers with application in drug delivery. J Funct Biomater Switzerland. 2012;3:615–41.
Zhao L, Yang G, Shi Y, Su C, Chang J. Co-delivery of Gefitinib and chloroquine by chitosan nanoparticles for overcoming the drug acquired resistance. J Nanobiotechnology England. 2015;13:57.
Salatin S, Yari KA. Overviews on the cellular uptake mechanism of polysaccharide colloidal nanoparticles. J Cell Mol Med England. 2017;21:1668–86.
Prokop A, Davidson JM. Nanovehicular intracellular delivery systems. J Pharm Sci Elsevier. 2008;97:3518–90.
Li Q, Liu C-G, Yu Y. Separation of monodisperse alginate nanoparticles and effect of particle size on transport of vitamin E. Carbohydr Polym England. 2015;124:274–9.
Acknowledgments
This research was supported by the Arkansas Bioscience Institute under the project: Development of an avian model for evaluation early enteric microbial colonization on the gastrointestinal tract and immune function.
Funding
The authors thank the CONACyT for the doctoral scholarship number 447447 and the financial support obtained through the program PAPIIT IN218115 of DGAPA-UNAM.
Author information
Authors and Affiliations
Contributions
Daniel Hernández-Patlán, Bruno Solís-Cruz, Mario Alberto Cano-Vega, Eric Beyssac, Ghislain Garrait, Guillermo Tellez, Raquel López-Arellano, and Gustavo R. Rivera-Rodriguez contributed to the overall study design and supervised all research. Daniel Hernández-Patlán, Bruno Solis-Cruz, and Mario Alberto Cano-Vega carried out the experiments and acquisition of data. Daniel Hernández-Patlán, Gustavo R. Rivera-Rodriguez, and Guillermo Tellez drafted and revised the first version of the manuscript. Daniel Hernández-Patlán, Bruno Solís-Cruz, Eric Beyssac, Ghislain Garrait, Raquel López-Arellano, Guillermo Tellez, and Gustavo R. Rivera-Rodriguez analyzed the data. Xochitl Hernandez-Velasco, Guillermo Tellez, and Gustavo R. Rivera-Rodriguez drafted the article and revised it critically for important intellectual content. Daniel Hernández-Patlán, Xochitl Hernandez-Velasco, and Guillermo Tellez were also responsible for the final editing of the manuscript. All the authors reviewed and finally approved the manuscript.
Corresponding author
Ethics declarations
Conflicts of Interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Hernandez-Patlan, D., Solis-Cruz, B., Cano-Vega, M.A. et al. Development of Chitosan and Alginate Nanocapsules to Increase the Solubility, Permeability and Stability of Curcumin. J Pharm Innov 14, 132–140 (2019). https://doi.org/10.1007/s12247-018-9341-1
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12247-018-9341-1