Microchannel emulsification study on formulation and stability characterization of monodisperse oil-in-water emulsions encapsulating quercetin
Graphical abstract
Introduction
Quercetin (3,3′,4′,5,7-pentahydroxyflavanone) is categorized as a flavonol and belongs to the family of flavonoids (Ross & Kasum, 2002). By definition, quercetin is an aglycone (lacking an attached sugar) with a brilliant citron yellow colour that is entirely insoluble in water, sparingly soluble in oil medium, and readily soluble in a variety of polar solvents (Kelly, 2011). The solubility of quercetin in the aqueous phase can be greatly improved by attaching glycosyl groups at hydroxyl positions (Hollman et al., 1999). Flavonols are present in many vegetables, flowers, nuts and fruits (Häkkinen, Kärenlampi, Heinonen, Mykkänen, & Törrönen, 1999). They are also abundant in a variety of medicinal plants, such as Ginko bioloba, Solanum trilobatum, and many others (Kelly, 2011). The estimated intake of flavonols ranges from 20 to 50 mg d−1. Most of the dietary intake is as flavonol glycosides of kaempferol, myricetin and quercetin (Cao, Zhang, Chen, & Zhao, 2010).
Quercetin exhibits a wide range of biological activities, including anticancer, antioxidant, antitoxic, antithrombotic, anti-ageing, metal chelating and antimicrobial activities (Borska et al., 2010, Kelly, 2011). Similarly, it has an impact on obesity, sleep and mood disorders (Joshi et al., 2005, Kelly, 2011). Recently, quercetin has been used in many sport supplements in order to reduce post-exercise immune system perturbations (Davis, Carlstedt, Chen, Carmichael, & Murphy, 2010). The bioavailability and absorption of quercetin depend upon the nature of the attached sugar, solubility modifications, and the types of emulsifiers used in different systems (Scholz & Williamson, 2007). Despite its significant biological activities, quercetin has very poor oral bioavailability. The main disadvantages of using quercetin in therapeutics and functional foods are its poor solubility in aqueous and oil media, very low bioavailability, poor permeability and crystallization at ambient temperatures (Borghetti et al., 2009, Pouton, 2006). To overcome these disadvantages, it is essential to develop an efficient delivery system for quercetin that improves its stability and release at the appropriate target site.
Different colloidal systems are there to encapsulate vital lipophilic compounds, including emulsions, solid lipid micro- and nano-particles, filled hydrogel particles and polymeric nano-particles (Flanagan and Singh, 2006, McClements and Rao, 2011). These colloidal delivery systems were formulated either with conventional emulsification tools or microfluidic devices (Vladisavljevic et al., 2013). In this study, we used microchannel emulsification (MCE) to encapsulate quercetin in different oil-in-water (O/W) emulsions. MCE is a promising technique for generating monodisperse emulsion droplets with a size variation of less than 5% (Kawakatsu, Kikuchi, & Nakajima, 1997). MCE devices consist of either parallel grooves and terraces or straight-through microholes (Kawakatsu et al., 1997, Kobayashi et al., 2002). The distinguishing features of MCE involve the absence of external shear forces during droplet generation and the droplet size being mainly determined by the MC geometry and composition of dispersed and continuous phase (Vladisavljevic, Kobayashi, & Nakajima, 2012). The droplet generation in MCE takes place due to spontaneous transformation of a dispersed phase passing through the MCs, as a result of the interfacial tension dominant on micron scales (Sugiura, Nakajima, Iwamoto, & Seki, 2001). MCE has been successfully applied to the preparation of simple and multiple emulsions, microspheres and microcapsules (Vladisavljevic et al., 2013). Many hydrophilic and lipophilic compounds have been encapsulated in these systems, such as β-carotene (Neves, Ribeiro, Kobayashi, & Nakajima, 2008), oleuropein (Souilem et al., 2014), γ-oryzanol (Neves, Ribeiro, Fujiu, Kobayashi, & Nakajima, 2008), l-ascorbic acid (Khalid et al., 2014b, Khalid et al., 2015a, Khalid et al., 2015b), ascorbic acid derivatives (Khalid et al., 2014a) and vitamin D (Khalid et al., 2015a, Khalid et al., 2015b).
The aim of this study was to design food grade O/W emulsions encapsulating quercetin using straight-through MCE. The present study investigated the effects of emulsifier type on the droplet generation characteristics and stability of emulsions encapsulating quercetin. Moreover, the effects of different dispersed phase composition on quercetin encapsulation were examined, together with the physical and chemical stability of the formulated emulsions. The results of this study improve the understanding of significant factors that influence the encapsulation, stabilization and utilization of crystalline bioactive compounds in food, cosmetics and pharmaceuticals.
Section snippets
Chemicals
3,3′,4′,5,7-pentahydroxyflavanone (quercetin) was procured from Nacalai Tesque, Inc. (Kyoto, Japan). Dimethyl sulfoxide, polyoxyethylene (20) sorbitan monolaurate (Tween 20, Hydrophilic-Lipophilic Balance (HLB) 16.7) and bovine serum albumin (BSA) were procured from Wako Pure Chemical Industries (Osaka, Japan). Sodium salt of colic acid with >97% (Na-cholate) was procured from Sigma Aldrich (St. Louis, MO, USA). The medium chain triacylglycerides (MCT, sunsoft MCT-7) composed of 25% capric acid
Effect of different emulsifiers on emulsion formulation
Emulsifier molecules play a critical role in the stability of oil droplets in MCE. The charge on the MC array chip surface and its electrostatic interactions with the emulsifiers must be kept in mind during MCE. Uniformly sized oil droplets can be generated from the MCs when the chip surface has a non-attractive interaction with the emulsifier molecules. Moreover, the stability of the droplets correlates with the type of emulsifier in the continuous phase and with whether it preferentially wets
Conclusions
The present study demonstrated the successful formulation of food-grade monodisperse O/W emulsions encapsulating quercetin through straight-through MCE. The results for the effect of different emulsifiers indicate that Tween 20 was the best selection as the emulsifier for this study. Successful droplet generation and monodispersity were achieved at a maximum of 0.4 mg ml−1 quercetin in an MCT oil as the dispersed phase. The selected operating parameters include Jd of 20–40 L m−2 h−1 and of
Acknowledgments
The first author acknowledges the fellowship from the University of Tokyo for studying at the University of Tokyo and National Food Research Institute, NARO of Japan.
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Present affiliation: Alliance for Research on North Africa, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8572, Japan; Algae Biomass and Energy System R&D Center, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8577, Japan; School of Agriculture, University of Management and Technology, Lahore, Pakistan.