Article pubs.acs.org/JAFC
Quercetin Nanosuspensions Produced by High-Pressure Homogenization Ayse Karadag,†,‡ Beraat Ozcelik,† and Qingrong Huang*,‡ †
Department of Food Engineering, Faculty of Chemical and Metallurgical Engineering, Istanbul Technical University, 34469 Maslak, Istanbul, Turkey ‡ Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, New Jersey 08901, United States ABSTRACT: High-pressure homogenization (HPH) was used to increase the water solubility of quercetin crystals, which exhibit antioxidant, anti-inflammatory, and anticancer properties but poor water solubility and oral bioavailability. The improved water solubility of quercetin by HPH treatment could be attributed to very fine suspensions produced in the nanometric range (∼400 nm) and loss of crystallinity caused by mechanical friction and stresses, which were verified by particle size measurements, differential scanning calorimetry (DSC), atomic force microscopy (AFM), and scanning electron microscopy (SEM) results. Easily water redispersible powders were fabricated by the combination of HPH treatment and spray-drying process when maltodextrin was used as a carrier agent. HPH-treated spray-dried powders exhibited higher antioxidant activities than nontreated samples through increased water dispersity in terms of radical scavenging activity, reducing ability, and oxygen radical absorbance capacity determinations. This study suggests that the combination of HPH treatment with spray-drying would be an excellent processing method for the development of quercetin-based functional food products. KEYWORDS: quercetin, nanosuspension, antioxidant activity, high-pressure homogenization (HPH), spray-drying
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lower than 1 μm.11 There are several physical processing methods such as jet or pearl mill micronization,12,13 precipitation,14 spray-drying, microfluidization,15,16 and highpressure homogenization (HGH).17,18 Although micronization techniques allow producing very fine suspensions, mostly they are not suitable for in vivo administration due to high polydispersity of products. The particle size should be in the nanometer range with little content of microparticles. Otherwise, the large particles can lead to embolism if they exceed a critical administered dose when injected in vivo.11,19 Among physical processing methods to produce nanosuspensions, HPH is a simple and highly recommended process with high efficiency, reproducibility, no need for organic solvents, and ease of scaling up in industry. In this process, a macrosuspension of drug particles is passed at high pressure through a narrow homogenization gap at a very high velocity. This technology can be applied to poorly water-soluble drugs.13,19−22 The present work aims to utilize HPH for formulating quercetin as a drug nanosuspension as a significant potential to enhance its water solubility. The effects of pressure and the number of processing cycles on particle size and solubility have been studied to achieve the optimized processing conditions. Production of dry formulations that have higher dispersity, fast dissolution rate, and increased antioxidant activities would facilitate their use in functional food formulations. Therefore, this study also aims to produce quercetin nanosuspensions in dried form by the combination of spray-drying with HPH.
INTRODUCTION Flavonoids are polyphenolic compounds that are commonly distributed in foods of plant origin. Among flavonoids, quercetin (QT, 3,3′,4′,5,7-pentahydroxyflavone), the major representative of the flavonol subclass, is a common dietary component. Particularly rich sources for quercetin are onions, apples, and tea.1,2 It has been demonstrated to possess a wide array of biological effects that are considered beneficial to health, including antioxidative, free radical scavenging, anticarcinogenic, anti-inflammatory, and antiviral activities.3−6 Recently, there have been reports that quercetin can inhibit the proliferation of multiple cancer cell types, including lung, colon cancer cells, prostate carcinoma, and pancreatic tumor cells, and promote cell apoptosis at micromolar concentrations.7 However quercetin’s poor solubility in water (0.17−7 μg/ mL), artificial gastric juice (5.5 μg/mL), and artificial intestinal juice (28.9 μg/mL) has limited its absorption upon oral adminstration.8 After oral administration of quercetin aglycone, only in a relatively few studies was it detected in plasma and urine.4−9 Together with membrane permeability, drug solubility is among the key determinants for oral bioavailability. For that reason, approaches to improve the water solubility of many nutraceuticals are of great importance in functional food and drug formulations.10 An alternative procedure to improve the solubility of a drug is the use of physical processing methods that increase the surface area and wettability of drug particles by means of particle size reduction or generation of amorphous states of drugs. The rate of dissolution is proportional to the surface area. Owing to the increased surface to volume ratio of the nanocrystals, an increase in saturated solubility and very fast dissolution rate can be seen, especially for particles of sizes © 2014 American Chemical Society
Received: Revised: Accepted: Published: 1852
September 11, 2013 January 13, 2014 January 28, 2014 January 28, 2014 dx.doi.org/10.1021/jf404065p | J. Agric. Food Chem. 2014, 62, 1852−1859
Journal of Agricultural and Food Chemistry
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Article
presence of residual fine solid particles, if not sedimented by the centrifugation method applied, may affect the UV−vis measurement. Nevertheless, particle size measurements after centrifugation showed that the mean sizes of residual solid particles dispersed in the liquid were always
