Characterizations of food-derived ellagic acid-Undaria pinnatifida polysaccharides solid dispersion and its benefits on solubility, dispersity and biotransformation of ellagic acid
Graphical abstract
Introduction
Ellagic acid (EA, 2,3,7,8-tetrahydroxychromeno [5,4,3-cde] chromene-5, 10-dione) is a natural polyphenolic compound which is mainly available in fruits and nuts such as pomegranates, blackcurrants, cranberries, strawberries, walnuts and chestnut (Mohammadinejad et al., 2021). For the past few years, increasing studies have proved that EA possessed various pharmacological properties including anticarcinogenic, atheroprotective, antioxidant, anti-inflammatory and antidiabetic effects (Ríos et al., 2018). Due to the various biological activities, EA is often consumed as a drug or common dietary supplement in treatment of cancer and other disorders in certain countries (Mansouri et al., 2014, Xue et al., 2022). However, the actual medication effect of EA was mainly limited by two aspects. On the one hand, the hydrophobic feature not only affected its manufacturing application but also led to poor bio-availability and unstable effects. On the other hand, the consumed EA were mostly transformed into urolithins by intestinal flora fermentation to elicit biological functions in vivo (Gaya et al., 2016), therefore, confined biotransformation process also resulted in unstable effects. Currently, plentiful delivery approaches to increase EA solubility have been developed to increase EA bioavailability in the systemic circulation. For example, Zheng et al. fabricated a drug delivery system including formulation of 10 % ethyl oleate, 67.5 % Tween 80, 22.5 % polyethylene glycol 400, 0.5 % polyvinylpyrrolidone K30 (PVP K30), and 4 mg/g EA. And the results showed that EA-loaded exhibited better antioxidant ability in comparison with pure EA (Zheng et al., 2019). Diao et al. found α-lactalbumin could improve the solubility and antioxidant property of EA by forming a complexation (Diao et al., 2022). While few investigations studied the delivery system to enhance EA biotransformation process.
On account of the low aqueous solubility and dispersibility of hydrophobic polyphenolic compounds, their microbial biotransformation is often hindered with limited substrate accessibility to microorganisms. To solve the aforementioned challenge, many biotransformation systems have been proposed. Rocío et al. found EA dissolved with 1 % DMSO in medium was better metabolized and offered the possibility of other metabolic intermediates than in the absence of DMSO, prompting that EA conversion was affected by its solubility property (García-Villalba et al., 2013). Zhou et al. used polyoxyethylene (10) nonylphenyl ether (TX-40), a nonionic surfactant, to enhance phytosterol solubility during 9α-OH-AD biotransformation, and the results showed the product yield increased 217.2 % over controls (Zhou et al., 2019). Although organic solvents and other additives increase substrate solubility, their high toxicity may limit the microorganism growth during the biotransformation while organic solvents are undesirable in the food manufacturing industry. Therefore, it is essential to exploit more biocompatible and effective substrate supply approaches for microbial biotransformation.
Solid dispersion (SD) formulation can prevent the growth of crystal nuclei of insoluble materials and disperse them into amorphous or metastable microcrystalline state in water-soluble carriers for solubility enhancement. It has been widely applied to improve rate of dissolution and oral absorption of poorly water-soluble drugs in the pharmaceutical field. Carriers play a crucial part in SD formulation (Tran & Tran, 2020). The common carriers used are synthetic polymer such as PVP, PEG, poloxamer, etc (Tekade & Yadav, 2020). In recent years, natural polymers, for example polysaccharides, cyclodextrin and so on, are attracting more interests as the carriers than the synthetic ones because of their non-toxic nature, easy availability and favorable bioactivity (Li et al., 2021, Vipin et al., 2016). Undaria pinnatifida is an edible brown alga that is distributed mainly in Far East Asia including Korea, China, and Japan (Han et al., 2016). The natural Undaria pinnatifida polysaccharides (UPP) are safe, nontoxic and edible with high viscosity, biodegradability, biocompatibility, and favorable biological activities, which may be the desired carrier of EA (Zeng et al., 2022). Furthermore, in the previous study, it was found that UPP intervention could markedly change the intestinal microflora composition by increasing the relative abundance of beneficial bacteria and decreasing the relative abundance of pathogenic bacteria in rats (Li et al., 2021). The remarkable ability of UPP to regulate the intestinal flora might ulteriorly improve EA microbial biotransformation. Hence, the current study formulated the food-derived ellagic acid-Undaria pinnatifida polysaccharides solid dispersion (EA/UPP SDs), with the goal of achieving better solubility, dispersibility and biotransformation efficacy. The EA/UPP SDs were characterized by solubility and redissolution determination, particle size and polydispersity index (PDI) determination, fourier transform infrared (FT-IR), UV–vis spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis and differential scanning calorimetry (TG-DSC), and scanning electron microscopy (SEM). In addition, anaerobic fermentations in vitro were also carried to study whether the UPP carrier could enhance the biotransformation of EA.
Section snippets
Material and reagent
Undaria pinnatifida was purchased from Qingdao Fuxingxiang Import & Export Co., ltd, Shandong, China. Raw Undaria pinnatifida was washed with running tap water and then immersed in 95 % ethanol overnight to remove the impurities. The dried raw materials were pulverized, sieved, and stored at room temperature for further use.
EA (purity ≥ 90 %) was purchased from Xi’an Mixianer Biotechnology Co., ltd. (Shaanxi, China). EA standard (purity ≥ 96 %), urolithin C standard (purity ≥ 95 %) and
Water dispersion behaviors of EA/UPP SDs
Fig. 1A-B showed the visual observation of EA/UPP SDs and EA redissolved in water at the concentration of 0.1 % (w/v). Firstly, the fully soluble UPP solution appeared transparent and yellow without any sediments. The SDs and EA solution were opalescent, but the dispersity considerably varied. The solutions of EA milling and EA exhibited apparently worse dispersion behaviors when compared to other solutions. To clearly observe the status, we suctioned 100 μL above solution of each sample and
Conclusion
In present study, EA/UPP SDs were prepared by mechanochemical treatment. Compared with pure EA, EA/UPP SDs exhibited superior solubility and stably suspending status. EA/UPP SDs restrained EA self-aggregation, decreased the particle size and PDI, reduced crystallinity and maintained its dispersion in the aqueous solution. No new substances were generated during the ball milling preparation, and the structure of EA/UPP SDs was mostly maintained by hydrogen bonds and hydrophobic interactions. The
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.
Acknowledgement
This work was financially supported by Self-innovation Research Funding Project of Hanjiang Laboratory (No. HJL202104B001, HJL202101B002, HJL202101B005), Key-Area Research and Development Program of Guangdong Province (No. 2021B0707060001), Chaozhou Science and Technology Plan Project (No. 2020PT01), Opening Foundation Project of Hainan Key Laboratory of Storage and Processing of Fruits and Vegetables (No. HNGS202103).
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