Design and preparation of novel antioxidant and antibacterial films containing procyanidins and phycocyanin for food packaging.

The purpose of this study was to design a novel antioxidant and antibacterial film for food packaging using food-grade raw materials. The films were designed and fabricated based on carboxymethyl chitosan and pectin incorporated with procyanidins (PCs) and phycocyanin (Phy) by the tape casting method. The effects of different proportions of PCs and Phy on the properties and functions of the prepared films were studied. The results showed that the thickness of films could range from 55 to 70 µm, with dense network structure and uniform distribution of elements. Compared with C-Film group, the film loaded with PCs and Phy had lower water solubility and swelling rate, and higher tensile strength and elongation at break. FITR and XRD spectra revealed the molecular interaction mechanism among carboxymethyl chitosan, pectin, PCs and Phy, which could effectively endow the films with ultraviolet barrier properties. Moreover, the addition of PCs and Phy could effectively improve the antioxidant capacity and antibacterial effect of films, for example, the free radical scavenging abilities of most films were above 80% when the concentration of PCs was 40 µg mL-1. In view of these functional properties, the prepared film containing PCs and Phy have been successfully used in food packaging, which was proved by the preservation experiment of grapes. This study can provide theoretical and technical guidance for the preparation of biodegradable antibacterial films, and their application in the food packaging field.

Orally deliverable sequence-targeted astaxanthin nanoparticles for colitis alleviation.

Orally targeted strategy of anti-inflammatory agents has attracted tremendous attention for reducing highly health-care costs and enhancing the intervention efficiency of ulcerative colitis (UC). Herein, we developed a new kind of sequence-targeted astaxanthin nanoparticles for UC treatment. Astaxanthin nanoparticles were firstly designed by self-assembly method using (3-carboxypentyl) (triphenyl) phosphonium bromide (TPP)-modified whey protein isolate (WPI)-dextran (DX) conjugates. Subsequently, lipoic acid (LA) modified hyaluronic acid (HA) was coated on the surface of the nanoparticles by double emulsion evaporation method. Exhilaratingly, the constructed sequence-targeted astaxanthin nanoparticle exhibited excellent macrophages and mitochondria targeting ability, with a Pearson's correlation coefficient of 0.84 adstnd 0.92, respectively. In vivo imaging elucidated an obvious accumulation of the sequence-targeted nanoparticles in colon tissues in UC mice. Meanwhile, the reduction stimulus release features of astaxanthin were observed in the presence of 10 mM of glutathione (GSH) at pH 7.4. Most importantly, in vivo experiments indicated that sequence-targeted astaxanthin nanoparticles could markedly alleviate inflammation by moderating the TLR4/MyD88/NF-κB signaling pathway. What's more, the composition of gut microbiota and the production of short chain fatty acid were also improved upon the uptake of sequence-targeted astaxanthin nanoparticles. Our results suggested this novel astaxanthin nanoparticles, which showed sequence-targeted ability and reduction response feature, could be exploited as a promising strategy for effective UC treatment.

Engineering Milk-Derived Exosome for Enhancing Cellular Astaxanthin Delivery.

Astaxanthin (AST), a fat-soluble carotenoid, shows excellent antioxidant and anti-inflammatory activities, but its low biocompatibility and stability limit its application in the food industry. In this work, we constructed the targeted hyaluronic acid (HA)-modified milk exosome-based astaxanthin delivery system to improve the biocompatibility stability and targeted transport properties of astaxanthin. Nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR) showed that HA was efficiently modified onto the surface of the milk exosome by an amide condensation reaction. The fluorescence images showed that the targeted delivery system accumulated in RAW264.7 macrophages, and the targeting effect on inflammatory cells was significantly enhanced. Compared with free astaxanthin, the delivery system could enhance the cellular uptake of astaxanthin and alleviate the overproduction of reactive oxygen species significantly and the depolarization of mitochondrial membrane potential in a lipopolysaccharide-induced cellular model. The delivery system also notably inhibited the expression of IL-1ß, IL-6, and other inflammatory factors. Therefore, the targeted hyaluronic acid-modified milk exosome-based astaxanthin delivery system prevents the activation of macrophages and the production of inflammatory mediators and has the potential to apply to the prevention of chronic inflammatory diseases.

Facile synthesis of food-grade and size-controlled nanocarriers based on self-assembly of procyanidins and phycocyanin.

Nanocarriers provide the possibility to overcome the low solubility, poor stability, and low bioavailability of functional factors. However, most nanocarriers do not directly participate in the corresponding effects of functional factors, such as treating inflammatory bowel disease but lack the means to control their size accurately. Herein, nanocarriers were prepared by a one-pot method, using food-grade antioxidant procyanidins, vanillin, and phycocyanin as raw materials. The strategy involved the Mannich reaction among the phenolic hydroxyl groups of procyanidins, the aldehyde groups of vanillin, and the amino groups of phycocyanin. The obtained nanocarriers displayed controllable sizes ranging from 130 to 750 nm, showing good antioxidant capacity in scavenging free radicals and were biocompatible to Caco-2 cells and RAW 264.7 macrophages. Nanocarriers also exhibited an inhibitory effect on cell damage induced by acrylamide and H2O2. Moreover, the designed nanocarriers could be used for delivering active ingredients such as lutein, which showed a uniform spherical distribution, high encapsulation efficiency, and good biocompatibility. This work provides a facile synthesis method to prepare food-grade nanocarriers with functional properties, which can be potentially used in the delivery of functional factors.

A smart cauliflower-like carrier for astaxanthin delivery to relieve colon inflammation.

As a fat-soluble carotenoid, astaxanthin has excellent antioxidant and anti-inflammation biological activities, but its poor biocompatibility and low stability limit application of astaxanthin in the food industry. In this study, cauliflower-like carriers (CCs) were constructed based on caseinate, chitosan-triphenylphosphonium (TPP) and sodium alginate through an electrostatic self-assembly method to improve the biocompatibility, stability and targeting transport properties of astaxanthin. The smart CCs showed pH-response release and mitochondrial targeted characteristics. In vitro studies demonstrated that the CCs could improve the internalization of astaxanthin, and significantly inhibited the excessive production of reactive oxygen species and the depolarization of mitochondrial membrane potential caused by oxidative stress. In vivo studies revealed that the astaxanthin-loaded CCs could effectively relieve the colitis induced by dextran sodium sulfate and protect the integrity of the colon tissue structure. The astaxanthin-loaded CCs could significantly inhibit the expression of inflammation factors such as interleukin-1ß, interleukin-6, tumor necrosis factor alpha, cyclooxygenase-2, myeloperoxidase, inducible nitric oxide synthase, and nitric oxide. Moreover, the astaxanthin-loaded CCs could maintain the expression of zonula occludens-1, increase the abundance of Firmicutes and Lactobacillaceae in the intestine. In a word, the constructed astaxanthin delivery system provided a potential application for the oral uptake hydrophobic bio-activator in intervention of ulcerative colitis.

Current Advances in Multifunctional Nanocarriers Based on Marine Polysaccharides for Colon Delivery of Food Polyphenols.

Inflammatory bowel disease (IBD) has been considered as a chronic disease that is difficult to cure and needs lifelong treatment. Marine polysaccharides with good biocompatibility and biodegradability, mucoadhesion, sensitivity to external stimuli, and targeting ability can be used as wall materials for oral colon-targeted delivery of polyphenols in nutrition intervention of IBD. This manuscript reviewed the latest progress in the design, preparation, and characterization of marine polysaccharides-derived multifunctional nanocarriers for polyphenol colon delivery. Chitosan, sodium alginate, chondroitin sulfate, and hyaluronic acid were discussed in the preparation of polyphenol delivery systems. The design strategy, synthesis methods, and structure characterization of multifunctional polyphenol carriers including stimuli-responsive nanocarriers, mucoadhesive and mucus-penetrating nanocarriers, colon targeted nanocarriers, and bioactive compounds codelivery nanocarriers were reviewed in the alleviation of IBD. The research perspectives in the preparation and characterization of delivery carriers using marine polysaccharide as materials were proposed for their potential application in food bioactive components.

Zinc delivery system constructed from food-borne nanoparticles derived from Undaria pinnatifida.

Food-borne nanoparticles from Undaria pinnatifida (UPFNs) were prepared and successfully applied as nanocarriers for microelement zinc delivery. UPFNs were spherical nanoparticles with average sizes of about 4.07 ± 1.09 nm, which chelated with zinc ions through amino nitrogen and carboxyl oxygen atoms as characterized by X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and 1H nuclear magnetic resonance spectroscopy. Thermodynamic analysis revealed that the overall chelation process between UPFNs and zinc ions was a spontaneous enthalpy-driven endothermic reaction. Compared to zinc sulfate, UPFN-Zn2+ showed higher solubility both in phytic acid solution and the process of gastrointestinal digestion. Meanwhile, no obvious cytotoxicity was found in UPFNs and UPFN-Zn2+. Specifically, UPFN-Zn2+ could successfully rescue cell viability, DNA replication activity and restore cell proliferation ability in zinc-deficient cells induced by a specific zinc chelator TPEN. Overall, UPFNs might serve as efficient, stable, and safe nanocarriers for zinc delivery.

Preparation and characterization of glycosylated protein nanoparticles for astaxanthin mitochondria targeting delivery.

Novel mitochondria targeting nanocarriers were prepared using triphenylphosphonium bromide (TPP)-modified whey protein isolate (WPI)-dextran (DX) conjugates by self-assembly method for astaxanthin mitochondria targeting delivery. The nanocarriers of astaxanthin-loaded WPI-DX and astaxanthin-loaded TPP-WPI-DX were 135.26 and 193.64 nm, respectively, which exhibited a spherical structure and good dispersibility. The mitochondria targeting nanocarriers had good stability in the stimulated blood fluid. In vitro experiments indicated that the TPP-modified nanocarriers could effectively realize lysosomes escape, and specifically accumulate in the cell mitochondria. Simultaneously, the astaxanthin-loaded nanocarriers could significantly reduce reactive oxygen species generation produced from hydrogen peroxide, protect the normal levels of the mitochondrial membrane potential, and dramatically promote the vitality of leukemia cells in mouse macrophage (RAW 264.7) cells. The present study highlights the promising application of mitochondria targeting nanocarriers for enhanced delivery of astaxanthin.

Ultrasonic Self-Emulsification Nanocarriers for Cellular Enhanced Astaxanthin Delivery.

Oil in water (O/W) nanocarriers were prepared for cellular enhanced astaxanthin delivery using a (3-carboxypropyl) triphenylphosphonium bromide (TPP)-modified casein by an ultrasonic self-emulsification method. The nanocarriers of casein emulsion loaded with astaxanthin and casein modified by TPP emulsion encapsulated with astaxanthin were 227 and 543 nm, respectively, with a spherical shape. The thermal stability and resistance to ultraviolet (UV) radiation ability of astaxanthin were significantly improved after encapsulation by the nanocarriers. The fluorescence colocalization imaging proved an accumulated effect of astaxanthin encapsulated in casein emulsion nanocarriers modified by TPP. Meanwhile, the astaxanthin loaded on TPP-modified nanocarriers could significantly protect the mitochondrial membrane potential from depolarization in the normal rat kidney (NRK) cells after oxidative damage. The cell viability assay demonstrated that the astaxanthin loaded on TPP-modified nanocarriers could enhance the growth of NRK and RAW264.7 cells as compared with astaxanthin encapsulated by casein emulsion without TPP modification.

pH-Responsive Core-Shell Microparticles Prepared by a Microfluidic Chip for the Encapsulation and Controlled Release of Procyanidins.

The purpose of this study was to construct a delivery system using a microfluidic chip to protect procyanidins (PCs) and to achieve their pH-controlled release in simulated gastrointestinal fluid. The microfluidic chip was designed and fabricated to generate water-in-water-in-oil (W/W/O) templates for the preparation of sodium alginate/chitosan microparticles with a uniform size and core-shell structure, using an internal-external gelation method. Compared with free PCs, the stability of PCs embedded in microparticles was improved and a pH stimulus-responsive release of PCs from microparticles was observed under neutral pH conditions. The delivery system of microparticles was nontoxic and showed an inhibitory effect on the decrease of mitochondrial membrane potential in Caco-2 cells caused by H2O2 and acrylamide. This work provided a method for fabricating compact microfluidic chips to prepare a pH stimulus-responsive PCs delivery system with improved stability, which may have potential applications in the delivery of other nutrients.

Procyanidins-Loaded Complex Coacervates for Improved Stability by Self-Crosslinking and Calcium Ions Chelation.

The purpose of this work was to develop a facile strategy based on self-crosslinking between the core and wall materials in the coacervation system for effective procyanidins (PCs) encapsulation. The coacervates were constructed through the interaction of bioactive PCs, gelatin, and sodium alginate, followed by forming cationic bridge of sodium alginate-calcium ions to improve the stability of PCs. When the concentration of PCs and calcium ions were 6.25 and 0.24 mg/mL, respectively, the PC-loaded coacervates showed spherical shape with a size about 150 nm, and the microcapsulation efficiency and yield was 81.19 ± 1.47 and 87.86 ± 2.67%, respectively. The photothermal stability of PCs was effectively improved by embedding them in coacervates. The decrease of mitochondrial membrane potential in PC-12 cells induced by H2O2 was significantly inhibited by PC coacervates, demonstrating an improved protection effect of PCs after being encapsulated in coacervates.

Hydrophilic Food-Borne Nanoparticles from Beef Broth as Novel Nanocarriers for Zinc.

Food-borne nanoparticles (FNs) may be used as nanocarriers for metal ion chelation in micronutrient supplements. In this paper, the preparation and characterization of hydrophilic FNs were reported from beef broth cooked with a pressure cooker at 117 °C for different periods (30, 50, and 70 min) and their potential application as nanocarriers for zinc was investigated. The broth FNs are quasi-spherical with good water solubility and ultrasmall size, which can emit a strong sapphire color under 365 nm ultraviolet irradiation. X-ray photoelectron spectroscopy (XPS) analysis showed that there are carboxyl, amino, and hydroxyl groups on the FNs, which are useful for Zn(II) chelation. The vibration band of C═O at 1688 cm-1 in the infrared spectrum of FNs shifted to 1718 cm-1 after binding with Zn(II) ions, suggesting the participation of the carbonyl group in Zn(II) ion chelation. The appearance of Zn2p XPS peaks, at 1021.6 and 1045 eV for Zn(II)-FNs, clearly demonstrated the formation of Zn-O between the FNs and zinc ions. Biodistribution of FNs and the Zn(II)-FN complex in normal rat kidney cells demonstrated that they could easily enter normal rat kidney cells. A downfield was found for the signals of Zn(II)-FNs in 1H nuclear magnetic resonance spectroscopy and strongly suggested the binding of Zn(II) ions to FNs through carboxylic acid, hydroxyl, and amine groups. In addition, no obvious cytotoxicity was found for Zn(II)-FNs compared to zinc (ZnSO4) and commercial zinc gluconate. The results revealed that the FNs from beef broth may have a potential as nanocarriers for zinc chelation.