Ultrasound-based one-step fabrication of nobiletin particle: A facile stabilization strategy
Introduction
Nowadays, with the development of extraction technology and purification technique, great importance has been attached to food functional components derived from plants. Among them, NOB is a notable bioactive substance, abundant in citrus peel and some Chinese medicinal herbs (Cui et al., 2019). There has been plenty of scientific research focusing on its health benefits, including antioxidants, anti-inflammatory, anti-diabetic, against Alzheimer’s and Parkinson’s disease (Chen et al., 2017, Nakajima and Ohizumi, 2019). However, due to its chemical structure, NOB possesses the property of poor water solubility and crystallization at both ambient and body temperature, which, to a large extent, negatively affects its production, storage, and human absorption (Zhang et al., 2020). Specifically, weak stability in water-based formulation significantly reduces its addition amount and shelf-life when applied into food products. In the meantime, crystal state hindered the absorption and utilization in gastrointestinal tract.
As a matter of fact, some attempts have already been made for a feasible and effective stabilization strategy. (Zhao, Yang, & Xie, 2019). Apart from practical synthesis of its desmethyl derivatives (Asakawa et al., 2019), encapsulation is a commonly applied strategy for NOB stabilization. Existing studies have covered almost all common formulations (Kesharwani, Mallya, Kumar, Jain, Sharma, & Dey, 2020), including emulsion (Chen et al., 2015, Lei et al., 2017), liposome (Huang, Dou, Wu, Sun, Wang, & Huang, 2017), microcapsule based on plant exine capsules (Wu et al., 2018, Wu et al., 2019), and nanoparticle coated by zein (Wu, Wang, Wang, Li, & Liang, 2019). Without a doubt, each of them has their own advantage as well as imperfection. In summary, the two demands, namely strong storage stability and high load capacity, seem to be difficult to reach at the same time in one stabilization system (Sun et al., 2018, Wu et al., 2019). As a result, it is urgent to seek for a new system meeting both requirements.
Inspired by the concept of nanocrystal (Jacobs, Kayser, & Müller, 2000) and sonocrystallisation (Prasad, & Dalvi, 2020), anti-solvent method combined with ultrasound technique offers a new direction of research on stabilization system. In terms of hydrophobic crystalline bioactive components, if we can make direct use of their original crystalline form, the loading efficiency will be 100% in theory (Müller, Gohla, & Keck, 2011). Furthermore, on one hand, nanocrystal formulation makes progress in safety and oral bioavailability (Hou, Shao, Fu, Li, Sun, & He, 2017), for its reduced amount of coating material as well as increased surface ratio for contact with intestinal wall. On the other hand, ultrasonic treatment with its multi-function, containing acoustic cavitation, thermal effect, mechanical effect, etc., guarantees particle formation and controls particles’ size (Nalesso, Bussemaker, Sear, Hodnett, & Lee, 2020). However, co-processed by both treatments mentioned above, the functional compounds still tend to crystallize out rapidly after a short-term storage, reducing the equilibrium solubility of the whole system (Bao et al., 2020, Su et al., 2015). Hence it is desirable to find out a powerful coating method to help the aggregates formed by the anti-solvent process achieve long-term stabilization.
The discovery of this metal-phenolic networks (MPNs) seems to provide a solution for this dilemma. MPNs was originally based on the coating potential of natural plant polyphenols found in traditional food and beverage, such as tea, chocolate, and wine (Sileika, Barrett, Zhang, Lau, & Messersmith, 2013). The dynamic interaction between phenolic and metal ions enables it to display more functional characteristics (Ejima, Richardson, & Caruso, 2017). To be specific, owing to its advantage of rapid preparation, versatility, firm crosslinking network structure (Ejima et al., 2013), and negligible cytotoxicity, MPNs has been extensively introduced in clean water production, engineer nanomaterials, and biointerfaces as ionic stabilizer. Especially, it was known as a self-assembled material applied for hollow capsule design (Guo et al., 2014). Nevertheless, there has never been a study on its ability to prevent the precipitation of aggregates.
Herein, in this current study, a one-step path was built up to fabricate NOB-loaded nanocrystal complexes based on a synthesis process, which is depicted in Fig. 1A. This synthesis overall combined anti-solvent method with ultrasonic treatment. At the same time, the selected MPNs consisted of tannic acid (TA) together with metal ions as wall materials, intended to provide high loading capacity and long-term stability. TA is a kind of tannin with a high molecular weight. Metal ions selected are all common in life and the amount, especially those of three-valent iron ions (FeIII) and aluminum ions (AlIII), were guaranteed to be lower than the safe dosage. The optimization of the system is mainly achieved by adjusting the type and content of each raw material. In what follows, the specific roles respectively played by these two coating parts will be discussed in detail. The physicochemical properties of particles, especially the potential ability to be resuspended after centrifugal, was characterized by dynamic light scattering and electron microscope. Additionally, in vitro experiment confirmed potential ability of effective release in the intestinal condition. In conclusion, our study proposed a facile stabilization method as preliminary attempt to overcome some bottle necks in storage, processing and oral delivery of NOB, a representative of hydrophobic bioactive compounds.
Section snippets
Material
NOB was purchased from Shanxi HuiKe Botanical Development Co., Ltd. (Xi’an, China, Purity ≥ 98%). TA was procured from Aladdin Chemistry Co., Ltd. (Shanghai, China). MOPS was acquired from Genview (USA). Except from HPLC Grade acetonitrile and acetic acid bought from Fisher Scientific Co., Ltd. (USA), all the other chemicals were of analytical grade, got from Sinopharm Chemical Reagent Co., Ltd. (Shanghai, China). Aqueous solutions applied in all experiments were double deionized (DDI) by a
Optimization on ultrasound time and metal ion variety
Z-average size, PDI and zeta potential of particles were taken as parameters for particle optimization. As depicted in Fig. 1B & C, sonication time and species of composited metal ions had a significant influence on ultimate particle formulation. The mean particle size gradually decreased with processing time, and after that it rose again, probably due to the compound action of cavitation and shock waves during ultrasound treatment. To be specific, the cavitation bubbles provided more numbers
Conclusion
In conclusion, a facile stabilization method for NOB was described based on encapsulation and self-assembly technology. Ultrasonication and MPNs played a decisive part in the course of particle formation. Especially, MPNs made of TA and metal ions could deposit on the surface of anti-solvent NOB particles to regulate crystal growth and achieve the higher acid stability as well as effective release in intestinal condition. Moreover, the advantages of the entire stabilization system lie in
CRediT authorship contribution statement
Xinyi Wang: Conceptualization, Methodology, Writing – original draft, Data curation, Writing - review & editing. Bin Zhou: Methodology, Investigation, Resources, Writing - review & editing. Di Wu: Conceptualization, Methodology, Data curation, Writing - review & editing. Xiaojuan Chen: Methodology. Bin Li: Conceptualization, Supervision, Project administration. Ling Wang: Methodology, Supervision, Project administration. Hongshan Liang: Conceptualization, Supervision, Project administration,
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
This work was financially supported by National Natural Science Foundation of China (Grant No. 31801586). The authors would like to express their sincere thanks to colleagues of Key Laboratory of Environment Correlative Dietology of Huazhong Agricultural University for offering kind helps.
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