Statistical Optimization of Production Conditions of Polycaprolactone-Chitosan-Curcumin Particles

Document Type: Research Paper

Authors

1 School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran

2 Department of Pharmacognosy and Pharmaceutics, Institute of Medicinal Plants, ACECR, Karaj, Iran

Abstract

Curcumin is an herbal plant with great therapeutic applications. Although it is useful in treating several diseases, its low solubility in water and low bioavailability in living systems are limiting factors in using curcumin as a medicine. One way to overcome these shortcomings is the production of curcumin micro/nano particles. In this research, the particles of curcumin loaded with polycaprolactone (PCL)/chitosan were synthesized by the electrospray technique. To obtain the optimal conditions, statistical optimization was carried out through Response Surface Method (RSM). The effect of flow rate, polymer concentration and PCL weight percentage on solution properties, mean particle size and particle size distribution were investigated. According to experimental results, the optimal size (471 nm) and size distribution (103) of particles were found at the lowest level of polymer concentration (2%) and flow rate (0.25 ml/hr) and the highest level of PCL weight percentage (80%). Thus, the result of this study can be used to improve the quality of curcumin based medicine.

Keywords


[1] Yallapu, M.M., Jaggi, M. and Chauhan, S. C. (2012). “Curcumin nanoformulations: a future nanomedicine for cancer.” Drug Discovery Today, Vol. 17, No. 1-2, pp. 71-80.

[2] Misra, R., Acharya, S. and Sahoo, S. K. (2010). “Cancer nanotechnology: application of nanotechnology in cancer therapy.” Drug Discovery Today, Vol. 15, No. 19-20, pp. 842-850.

[3] Maheshwari, R. K., Singh, A.K., Gaddipati, J. and Srimal, R. C. (2006). “Multiple biological activities of curcumin:” a short review. Life Sciences, Vol. 78, No. 18, pp. 2081-2087.

[4] Vogel, H. A. and Pelletier, J. (1815). “Curcumin-biological and medicinal properties.” J. Pharma, Vol. 2, No. 50, p. 24.

[5] Menon, V. P. and Sudheer, A. R. (2007). Antioxidant and anti-inflammatory properties of curcumin, “The molecular targets and therapeutic uses of curcumin in health and disease.” Vol. 595, pp. 105-125. Springer. Boston.

[6] Goel, A., Kunnumakkara, A. B. and Aggarwal, B.B. (2008). “Curcumin as “Curcumin”: from kitchen to clinic.” Biochemical Pharmacology, Vol. 75, No. 4, pp. 787-809.

[7] Masuda, T., Maekawa, T., Hidaka, K., Bando, H. Takeda, Y., and Yamaguchi, H. (2001). “Chemical studies on antioxidant mechanism of curcumin: analysis of oxidative coupling products from curcumin and linoleate.” Journal of Agricultural and Food Chemistry, Vol. 49, No. 5, pp. 2539-2547.

[8] Miquel, J., Bernd, A., Sempere, J. M., Dıaz-Alperi, J. And Ramırez, A. (2002). “The curcuma antioxidants: pharmacological effects and prospects for future clinical use. A review.” Archives of Gerontology and Geriatrics, Vol. 34, No. 1, pp. 37-46.

[9] Kikuchi, H., Kuribayashi, F., Kiwaki, N. and Na-kayama, T. (2010). “Curcumin dramatically enhances retinoic acid-induced superoxide generating activity via accumulation of p47-phox and p67-phox proteins in U937 cells.” Biochemical and Biophysical Research Communications, Vol. 395, No. 1, pp. 61-65.

[10] Srimal, R. C. and Dhawan, B. N. (1973). “Pharmacology of diferuloyl methane (curcumin), a non‐steroidal anti‐inflammatory agent.” Journal of Pharmacy and Pharmacology, Vol. 25, No. 6, pp. 447-452.

[11] Agarwal, B. B. and Harikumar, K. B. (2009). “Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases.” The International Journal of Biochemistry & Cell Biology, Vol. 41, No. 1, pp. 40-59.

[12] Weber, W. M., Hunsaker, L. A., Abcouwer, S.F., Deck, L.M. and Vander Jagt, D. L. (2005). “Anti-oxidant activities of curcumin and related enones.” Bioorganic & Medicinal Chemistry, Vol. 13, No. 11, pp. 3811-3820.

[13] Dikshit, M., Rastogi, L., Shukla, R. and Srimal, R.C. (1995). “Prevention of ischaemia-induced biochemical changes by curcumin & quinidine in the cat heart.” The Indian Journal of Medical Research, Vol. 101, pp. 31-35.

[14] Nirmala, C. and Puvanakrishnan, R. (1996). “Protective role of curcumin against isoproterenol induced myocardial infarction in rats.” Molecular and Cellular Biochemistry, Vol. 159, No. 2, pp. 85-93.

[15] Venkatesan, N. (1998). “Curcumin attenuation of acute adriamycin myocardial toxicity in rats.” British Journal of Pharmacology, Vo. 124, No. 3, pp. 425-427.

[16] Rao, C. V., Rivenson, A., Simi, B. and Reddy, B. S. (1995). “Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compound.” Cancer Research, Vol. 55, No. 2, pp. 259-266.

[17] Kuttan, R., Sudheeran, P. C., and Josph, C. D. (1987). “Turmeric and curcumin as topical agents in cancer therapy.” Tumori Journal, Vol. 73, No. 1, pp. 29-31.

[18] Shishodia, S., Chaturvedi, M.M. and Aggarwal, B. B. (2007). “Role of curcumin in cancer therapy.” Current Problems in Cancer, Vol. 31, No. 4, pp. 243-305.

[19] Tomren, M.A., Masson, M., Loftsson, T. and Tønnesen, H. H. (2007). “Studies on curcumin and curcuminoids: XXXI. Symmetric and asymmetric curcuminoids: stability, activity and complexation with cyclodextrin.” International Journal of Pharmaceutics, Vol. 338, No. 1-2, 27-34.

[20] Kurien, B. T., Singh, A., Matsumoto, H. and Scofield, R. H. (2007). “Improving the solubility and pharmacological efficacy of curcumin by heat treatment.” Assay and Drug Development Technologies, Vol. 5, No. 4, pp. 567-576.

[21] Nagavarma, B. V. N., Yadav, H. K., Ayaz, A., Vasudha, L. S., and Shivakumar, H. G. (2012). “Different techniques for preparation of polymeric nanoparticles-a review.” Asian Journal of Pharmaceutical and Clinical Research, 5(3), 16-23.

[22] Zambaux, M. F., Bonneaux, F., Gref, R., Main-cent, P., Dellacherie, E., Alonso, M. J. and Vigneron, C. (1998). “Influence of experimental parameters on the characteristics of poly (lactic acid) nanoparticles prepared by a double emulsion method.” Journal of Controlled Release, Vol. 50, No. 1-3, pp. 31-40.

[23] Jain, R. A. (2000). “The manufacturing techniques of various drug loaded biodegradable poly (lactide-co-glycolide) (PLGA) devices.” Biomaterials, Vol. 21, No. 23, pp. 2475-2490.

[24] McCarron, P.A., Donnelly, R.F. and Marouf, W. (2006). “Celecoxib-loaded poly (D, L-lactide-co-glycolide) nanoparticles prepared using a novel and controllable combination of diffusion and emulsification steps as part of the salting-out procedure.” Journal of Microencapsulation, Vol. 23, No. 5, pp. 480-498.

[25] Soppimath, K. S., Aminabhavi, T. M., Kulkarni, A. R. and Rudzinski, W. E. (2001). “Biodegradable polymeric nanoparticles as drug delivery devices.” Journal of Controlled Release, Vol. 70, No. 1-2, pp. 1-20.

[26] Scholes, P. D., Coombes, A. G. A., Illum, L., Daviz, S. S., Vert, M. and Davies, M.C. (1993). “The preparation of sub-200 nm poly (lactide-co-glycolide) microspheres for site-specific drug delivery.” Journal of Controlled Release, Vol. 25, No. 1-2, pp. 145-153.

[27] Rietveld, I. B., Kobayashi, K., Yamada, H. and Matsushige, K. (2006). “Electrospray deposition, model, and experiment: Toward general control of film morphology.” The Journal of Physical Chemistry B, Vol. 110, No. 46, pp. 23351-23364.

[28] Bagheri-Tar, F., Sahimi, M. and Tsotsis, T. T. (2007). “Preparation of polyetherimide nanoparticles by an electrospray technique.” Industrial & Engineering Chemistry Research, Vol. 46, No. 10, pp. 3348-3357.

[29] Jaworek, A. (2007). “Micro-and nanoparticle production by electrospraying.” Powder Technology, Vol. 176, No. 1, pp. 18-35.

[30] Jaworek, A. T. S. A., and Sobczyk, A. T. (2008). “Electrospraying route to nanotechnology: An overview.” Journal of Electrostatics, Vol. 66, No. 3-4, pp. 197-219.

[31] Chakraborty, S., Liao, I. C., Adler, A. and Leong, K.W. (2009). “Electrohydrodynamics: a facile technique to fabricate drug delivery systems.” Advanced Drug Delivery Reviews, Vol. 61, No. 12, pp. 1043-1054. 

[32] Jaworek, A. and Krupa, A. (1999). “Classification of the modes of EHD spraying.” Journal of Aerosol Science, Vol. 30, No. 7, pp. 873-893.

[33] Zhang, S. and Kawakami, K. (2010). “One-step preparation of chitosan solid nanoparticles by electrospray deposition.” International Journal of Pharmaceutics, Vol. 397, No. 1-2, pp. 211-217.

[34] Hogan Jr, C. J., Yun, K. M., Chen, D. R., Lenggo-ro, I. W., Biswas, P. and Okuyama, K. (2007). “Controlled size polymer particle production via electrohydrodynamic atomization.” Colloids and Surfaces A: Physicochemical and Engineering Aspects, Vol. 311, No. 1-3, pp. 67-76.

[35] Ijsebaert, J. C., Geerse, K. B., Marijnissen, J. C., Lammers, J. W. J., and Zanen, P. (2001). “Electro-hydrodynamic atomization of drug solutions for inhalation purposes.” Journal of Applied Physiology, Vol. 91, No. 6, pp. 2735-2741.

[36] Zarchi, A. A. K., Abbasi, S., Faramarzi, M. A., Gilani, K., Ghazi-Khansari, M. and Amani, A. (2015). “Development and optimization of N-Acetylcysteine-loaded poly (lactic-co-glycolic acid) nanoparticles by electrospray.” International Journal of Biological Macromolecules, Vol. 72, pp. 764-770.

[37] Liu, J., Xu, L., Liu, C., Zhang, D., Wang, S., Deng, Z. and Ma, J. (2012). “Preparation and characterization of cationic curcumin nanoparticles for improvement of cellular uptake.” Carbohydrate Polymers, Vol. 90, No. 1, pp. 16-22.

[38] Steyaert, I., Van der Schueren, L., Rahier, H. and De Clerck, K. (2012). “An alternative solvent system for blend electrospinning of polycaprolactone/chitosan nanofibres.” Macromolecular Symposia. Vol. 321, No. 1, pp. 71-75.

[39] Van der Schueren, L., Steyaert, I., De Schoenmaker, B. and De Clerck, K. (2012). “Poly-caprolactone/chitosan blend nanofibres electro-spun from an acetic acid/formic acid solvent system.” Carbohydrate Polymers, Vol. 88, No. 4, pp. 1221-1226.

[40] Chawla, J. S. and Amiji, M. M. (2002). “Biodegradable poly (ε-caprolactone) nanoparticles for tumor-targeted delivery of tamoxifen.” International Journal of Pharmaceutics, Vol. 249, No. 1, pp. 127-138.

[41] Ilium, L. (1998). “Chitosan and its use as a pharmaceutical excipient.” Pharmaceutical Research, Vol. 15, No. 9, pp. 1326-1331.

[42] Rinaudo, M. (2006). “Chitin and chitosan: properties and applications. Progress in Polymer Science.” Vol. 31, No. 7, pp. 603-632.

[43] Wu, L., Li, H., Li, S., Li, X., Yuan, X., Li, X. and Zhang, Y. (2010). “Composite fibrous membranes of PLGA and chitosan prepared by coelectrospinning and coaxial electrospinning.” Journal of Biomedical Materials Research Part A: An Official Journal of The Society for Bio-materials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials, Vol. 92, No. 2, pp. 563-574.

[44] Hartman, R. P. A., Brunner, D. J., Camelot, D. M. A., Marijnissen, J. C. M., and Scarlett, B. (2000). “Jet break-up in electrohydrodynamic atomization in the cone-jet mode.” Journal of Aerosol Science, Vol. 31, No. 1, pp. 65-95.

[45] Ganan-Calvo, A. M., Davila, J., and Barrero, A. (1997). “Current and droplet size in the electrospraying of liquids. Scaling laws.” Journal of Aerosol Science, Vol. 28, No. 2, pp. 249-275.

[46] Enayati, M., Ahmad, Z., Stride, E., and Edirisinghe, M. (2010). “Size mapping of electric field-assisted production of polycaprolactone particles.” Journal of The Royal Society Interface, Vol. 7 No. Suppl 4, pp. S393-S402.

[47] Lee, Y. H., Mei, F., Bai, M. Y., Zhao, S., and Chen, D. R. (2010). “Release profile characteristics of biodegradable-polymer-coated drug particles fabricated by dual-capillary electrospray.” Journal of Controlled Release, Vol. 145, No. 1, pp. 58-65.

[48] Mohan, P. K., Sreelakshmi, G., Mura-leedharan, C. V. and Joseph, R. (2012). “Water soluble complexes of curcumin with cyclodextrins: Characterization by FT-Raman spectroscopy.” Vibrational Spectroscopy, Vol. 62, pp. 77-84.

[49] Elzein, T., Nasser-Eddine, M., Delaite, C., Bi-stac, S. and Dumas, P. (2004). “FTIR study of poly-caprolactone chain organization at interfaces.” Journal of Colloid and Interface Science, Vol. 273, No. 2, pp. 381-387.

[50] Jayasree, A., Sasidharan, S., Koyakutty, M., Nair, S., and Menon, D. (2011). “Mannosylated chitosan-zinc sulphide nanocrystals as fluorescent bioprobes for targeted cancer imaging.” Carbohydrate Polymers, Vol. 85, No. 1, pp. 37-43.