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International Journal of Nanomedicine Dovepress open access to scientific and medical research Open access Full Text article OrIgINal research Formation of curcumin nanoparticles via solution- enhanced dispersion by supercritical cO2 Zheng Zhao1,3 Maobin Xie2 Yi li2 aizheng chen4 gang li5 Jing Zhang2 huawen hu2 Xinyu Wang1,3 shipu li1,3 1state Key lab of advanced Technology for Materials synthesis and Processing, Wuhan University of Technology, Wuhan, People’s republic of china; 2Institute of Textiles and clothing, The hong Kong Polytechnic University, hong Kong; 3Biomedical Materials and engineering research center of hubei Province, Wuhan University of Technology, Wuhan, People’s republic of china; 4college of chemical engineering, huaqiao University, Xiamen, People’s republic of china; 5National engineering laboratory for Modern silk, college of Textile and clothing engineering, soochow University, suzhou, People’s republic of china Abstract: In order to enhance the bioavailability of poorly water-soluble curcumin, solution- enhanced dispersion by supercritical carbon dioxide (CO2) (SEDS) was employed to prepare curcumin nanoparticles for the first time. A 24 full factorial experiment was designed to determine optimal processing parameters and their influence on the size of the curcumin nanoparticles. Particle size was demonstrated to increase with increased temperature or flow rate of the solution, or with decreased precipitation pressure, under processing conditions with different parameters considered. The single effect of the concentration of the solution on particle size was not significant. Curcumin nanoparticles with a spherical shape and the smallest mean particle size of 325 nm were obtained when the following optimal processing conditions were adopted: P =20 MPa, T =35°C, flow rate of solution =0.5 mL⋅min-1, concentration of solution =0.5%. Fou- rier transform infrared (FTIR) spectroscopy measurement revealed that the chemical composition of curcumin basically remained unchanged. Nevertheless, X-ray powder diffraction (XRPD) and thermal analysis indicated that the crystalline state of the original curcumin decreased after the SEDS process. The solubility and dissolution rate of the curcumin nanoparticles were found to be higher than that of the original curcumin powder (approximately 1.4 μg/mL vs 0.2 μg/mL in 180 minutes). This study revealed that supercritical CO2 technologies had a great potential in fabricating nanoparticles and improving the bioavailability of poorly water-soluble drugs. Keywords: curcumin, crystalline sate, dissolution rate, solubility Introduction Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1-6-heptadiene-3,5-dione), derived from the rhizome of the plant Curcuma longa, is a yellow-orange polyphenol com- pound. It is widely used as a spice, food preservative, and flavoring and coloring agent.1 Curcumin exhibits many therapeutic properties, including anti-inflammation, anti-oxidation and anticancer, anti-HIV, and antimicrobial activities. Besides, it can inhibit lipid peroxidation and scavenge superoxide anion, singlet oxygen, nitric oxide, and hydroxyl radicals.2 Despite displaying multiple beneficial pharmacological effects, curcumin suf- fers from extremely low aqueous solubility in water at physiological pH.3 The poor solubility of curcumin limits its absorption and results in low bioavailability.4 Many new drug delivery systems have been developed to increase the aqueous solubility and the bioavailability of curcumin by using a variety of drug carriers, including liposomes,5 phospholipid,6 cyclodextrin,7 chitosan nanoparticles,8 protein nanopar- ticles such as silk fibroin,9 zein,10 and bovine serum albumin,11 synthetic polymer nanoparticles such as PLGA,12,13 PCL-PEG-PCL triblock copolymer,14 and polymer nanofibers such as polyvinyl alcohol (PVA),15 poly-(ε-caprolactone),16 and zein.17 Another approach for improving the bioavailability of poorly water-soluble drugs is the micronization of these drugs. Decreasing the particle size of these drugs can correspondence: Yi li Institute of Textiles and clothing, The hong Kong Polytechnic University, 11 Yuk choi road, hung hom, hong Kong Tel +852 2766 6479 Fax +852 2773 1432 email tcliyi@polyu.edu.hk submit your manuscript | www.dovepress.com Dovepress http://dx.doi.org/10.2147/IJN.S80434 International Journal of Nanomedicine 2015:10 3171–3181 3171 © 2015 Zhao et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. 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