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Application of Protein-Polysaccharide Complex System in the Delivery of Active Ingredients

Chen Yaqiong , Song Hongdong , Wu Mao , Lu Yang , Guan Xiao

Progress in Chemistry ›› 2022, Vol. 34 ›› Issue (10) : 2267 -2282.

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Progress in Chemistry ›› 2022, Vol. 34 ›› Issue (10) : 2267-2282 DOI: 10.7536/PC220131
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Application of Protein-Polysaccharide Complex System in the Delivery of Active Ingredients
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Abstract

Protein-polysaccharide complex system, as the wall material of bioactive ingredient delivery systems, have multiple advantages that other materials such as synthetic polymers or inorganic materials do not have. The connection mode between protein and polysaccharide, the various forms of protein-polysaccharide complex forming delivery system are reviewed, and the development trend of this field is prospected. According to the structural characteristics of proteins and polysaccharides, the linking methods between the two are divided into non-covalent binding such as physical copolymerization, and covalent binding such as Maillard coupling, chemical cross-linking, and enzyme-catalyzed cross-linking. The binding mechanism of the above connection methods and the influencing factors are expounded. The delivery forms of active ingredients with protein polysaccharide complexes as wall materials are generally divided into emulsion systems, micelles, nanogels, molecular complexes, and shell-core structure systems. According to the characteristics and delivery requirements of different active ingredients, proteins and polysaccharides with suitable structures and types, as well as their connection methods and delivery systems, can be selected in a targeted manner. Moreover, with the gradual development and advancement of research, the development trend in this field is moving towards the direction of intelligence and targeting. At present, the protein-polysaccharide complexes delivery system of active ingredients still faces many challenges in system design, evaluation and application. This requires us to design and evaluate the delivery system of active ingredients in a safe and reasonable manner based on a more comprehensive and in-depth study of its impact and efficacy on active ingredients.

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protein-polysaccharide complex system / delivery system / binding method / targeted / active ingredients

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Chen Yaqiong, Song Hongdong, Wu Mao, Lu Yang, Guan Xiao. Application of Protein-Polysaccharide Complex System in the Delivery of Active Ingredients. Progress in Chemistry, 2022, 34(10): 2267-2282 DOI:10.7536/PC220131

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Contents

1 Introduction
2 Characteristics of protein and polysaccharide complex delivery vehicles
3 The binding mode of protein polysaccharides
3.1 Non-covalent binding
3.2 Covalent binding
4 Delivery system forms of protein-polysaccharide complex system for active ingredients
4.1 Emulsifying system
4.2 Micelles
4.3 Nanogel
4.4 Molecular complex
4.5 Shell-core particles
5 The development direction and trend of intelligence and targeting
6 Conclusion and outlook

1 Introduction

Bioactive substances are components that have beneficial effects on health by regulating physiological or cellular activities. Common bioactive substances include polyphenols, essential oils, carotenoids, vitamins, minerals, phytosterols, bioactive peptides and probiotics. Small amounts of these active compounds can exhibit a variety of beneficial effects on the human body, such as anticancer, neuroprotective, anti-inflammatory, antioxidant, and pain relief[1]. Food is the main source of bioactive substances. Developing functional foods containing bioactive substances or extracting bioactive ingredients from food for administration are promising ways to increase the intake of bioactive substances. However, simply incorporating bioactive substances into the food system in free form or direct administration will face many problems: (I) poor solubility, (ii) poor physical stability, (iii) poor chemical stability during food processing and storage, (iv) off-flavor, and (V) poor bioaccessibility and bioavailability[2][3][4,5][6][7]. Designing a suitable delivery system is an effective means to overcome these shortcomings. The design of the delivery system, first of all, is the selection of suitable delivery materials. At present, the materials used for the entrapment and delivery of drugs or active substances are mainly various polymers[8,9]. Among them, synthetic polymers are rarely used as delivery materials for bioactive substances because of their poor degradability and the potential safety hazards caused by the introduction of more chemicals in the preparation process[10]. Natural materials of food origin, such as polysaccharides and proteins, have become irreplaceable preferred embedding materials because of their safety, non-toxicity, good biocompatibility, and special application value in the delivery of bioactive substances due to various modifiable groups in their structures[11,12].
In this paper, the material characteristics of protein and polysaccharide complex delivery carriers, the binding mode of protein and polysaccharide in the delivery system, the form of the delivery system, and the development trend in this field are reviewed and prospected, which provides a reference for the safe and efficient delivery of active substances.

2 Characteristics of Protein and Polysaccharide Complex Delivery Carrier

Proteins and polysaccharides are natural biopolymers, which are abundant and have the potential to construct highly biocompatible, biosafe, and economically feasible delivery systems. Considering the diversity of proteins and polysaccharides and their unique structural and functional properties, the assembled protein and polysaccharide carriers can be established as universal delivery vehicles and can deliver bioactive substances for specific application purposes[2,4,5].
Delivery systems constructed by assembled protein and polysaccharide vectors have a variety of significant advantages over other vectors. First of all, there are many kinds of polysaccharides and proteins, and they contain many excellent adjustable and modifiable groups such as -OH, —NH2, -COOH, etc.It provides a structural guarantee for the combination of protein-polysaccharide-active substances and the establishment of the delivery system, and the protein-polysaccharide complex system becomes the target material for the delivery system to achieve high bioavailability and targeting modification because of these modifiable groups[13⇓~15][14,16,17]. Secondly, as a physical barrier, the delivery system constructed by protein and polysaccharide can protect the unstable bioactive compounds from the environment (light, oxygen, etc.), and the three-dimensional network can delay the release of bioactive components to achieve the purpose of long-term release of active substances[18]. Moreover, compared with single protein or polysaccharide, the protein-polysaccharide complex system as a carrier may have better stability, which is conducive to the efficient encapsulation, protection and release of bioactive compounds.For example, the participation of polysaccharides can provide steric hindrance to inhibit the aggregation of proteins, or to improve the solubility or adhesion of active substances as required[19][17]. In addition, some polysaccharides or proteins, due to their structural characteristics, have special delivery advantages, such as chitosan, which has special adhesion and penetration effects on intestinal epithelial cells due to its positive charge structure, and sodium alginate, which contains a large amount of — COOH, has become a natural pH-responsive controlled release material for contraction in the stomach and release in the small intestine[11][20].

3 Binding mode of protein and polysaccharide

The interaction between protein and polysaccharide plays an important role in the design of new delivery systems. Different bioactive substances have different delivery requirements, which have specific requirements for the selection of protein and polysaccharide materials and their combination. At present, generally speaking, the main binding modes of protein and polysaccharide are shown in Figure 1, which are basically divided into physical copolymerization, chemical crosslinking, biological binding and Maillard reaction. As a result of the construction of the system, non-covalent and covalent protein-polysaccharide complex systems are formed. Next, we will discuss in detail the various types of binding between proteins and polysaccharides.

3.1 Noncovalent binding

As far as the non-covalent binding between protein and polysaccharide is concerned, the interaction may include electrostatic interaction, hydrogen bonding and hydrophobic interaction, that is, the non-covalent binding between protein and polysaccharide is actually a physical condensation process. Coacervation refers to the metastable suspension of ion-rich droplets and is sometimes used to define spherical particles of colloidal droplets held together by hydrophobic forces, with Tiebackx being the first to report the term coacervation[16][21]. Condensation is divided into two types: simple condensation and complex condensation. Simple coagulation is achieved by changing different parameters to change the dehydration conditions of macromolecules, such as adjusting solvent conditions, adding microions, changing temperature and other parameters to make macromolecular solutes undergo condensed phase separation. At present, anti-solvent dispersion, ionic gelation, thermal gelation and other methods are widely used in the preparation of protein-polysaccharide complexes by simple coagulation. On the basis of these simple coagulation, protein-polysaccharide complexes can be prepared by electrostatic adsorption or several simple coagulation methods. Protein-polysaccharide complexes prepared by anti-solvent dispersion method are mostly used for alcohol-soluble vegetable protein, which uses the hydrophobic force of alcohol-soluble protein to form aggregates. Compared with animal protein, hydrophobic vegetable protein is cheaper and has the ability to continuously control drug release. For example, Song et al. Dissolved hordein and EGCG in isopropanol, and then dispersed them in water at a certain pH value and at a certain rate to obtain nanoparticles with an encapsulation efficiency of 91.2%.The chitosan solution was added dropwise to the solution containing the nanoparticles, and a certain amount of sodium tripolyphosphate was added as the ionic gelling agent of chitosan, combined with the anti-solvent method and the ionic gelling method to prepare the EGCG-loaded hordein-chitosan nanoparticles[22]. Similarly, zein was also dissolved in ethanol, and then added dropwise to the gelatinized carboxymethyl short amylose to form a ternary nanocomposite encapsulating the polypeptide, and on the basis of this structure, a chitosan layer was wrapped on the surface of the nanocomposite by electrostatic adsorption to optimize the oral availability of the polypeptide drug[23]. As far as the crosslinking agent ion of the ionic gel method is concerned, multivalent cations, such as Ca2+ and Fe3+, are often used to act on polysaccharides such as sodium alginate and pectin, while for chitosan, the above-mentioned sodium tripolyphosphate is the first choice[24,25].
Bungenberg and Kruyt first systematically studied the gum arabic-gelatin polysaccharide protein system and proposed the concept of complex coacervation, that is, in a solvent, two ions with opposite charges form two or more phases, and there are two polymers in each phase[16]. But the simultaneous physical mixing of protein and polysaccharide may lead to the existence of incompatible situations, which depend largely on the intrinsic properties of the polymer, as well as pH, protein/polysaccharide ratio, and ionic strength, where electrostatic interactions are the main driving force[26]. Clearly, pH is a major determinant of proteoglycan coacervation, and three key pH nodes are closely associated with soluble and insoluble protein-polysaccharide complex coacervates[27]. These three critical pH values, pHc, pHφ1, and pHφ2, are associated with the formation of soluble protein-polysaccharide complex coacervates, the initiation of insoluble protein-polysaccharide complex coacervates, and the dissociation into incompatible proteins and polysaccharides, respectively[28]. Except for a few polysaccharides such as chitosan, most polysaccharides have negative charges in a wide range, while the charge of protein depends on the pH value of the environment, as shown in Figure 2 (a). With the decrease of pH value, first, when pH > > pI, the protein is negatively charged, and the polysaccharide and protein repel each other; When pH ≈ pI, the protein is locally positively charged and weakly bound to the polysaccharide, forming a soluble complex aggregate (pHφ1);pH<. When the protein is positively charged, the polysaccharide is bound to the protein, forming an insoluble complex aggregate (pHφ1);pH< polysaccharide pKa, the turbidity decreases, and the insoluble complex aggregate dissolves (pHφ2).
As shown in fig. 3, in addition to the important role of pH, different parameters have a significant effect on the complex coacervation process, including material properties such as biopolymer molecular weight, total biopolymer concentration, biopolymer mix weight ratio, biopolymer charge density/biopolymer flexibility, and process parameters such as pH, pressure/agitation, temperature, and ionic strength[29,30]. Among them, ionic strength also has an important impact on several important pH nodes mentioned above, such as pHc, pHφ1, and pHφ2, as shown in Fig. 2 (B). Precise control of the protein/polysaccharide ratio and ionic strength is key to assembling proteins and polysaccharides, as these variables may determine the network structure of protein-polysaccharide complexes[28].

3.2 Covalent binding

The covalent binding of protein and polysaccharide, that is, the use of modifiable groups on protein and polysaccharide, mainly uses chemical and biological methods to link protein and polysaccharide to form protein-polysaccharide conjugates.

3.2.1 Chemical binding method

Proteins and polysaccharides contain carbonyl, carboxyl, amino, sulfhydryl and other active groups, which are excellent chemical reaction binding sites, and these reaction sites alone can carry out multiple chemical reactions.For example, click chemistry reaction, Ugi reaction, CNBr coupling method, disulfide bond coupling method and so on, which are common in the field of drug modification, but these reactions often require certain structural modification of polysaccharides or proteins.For example, click chemistry reaction needs to modify the structure of azide (-N ≡ N) and alkyne (-C ≡ C) on the structure of polysaccharide and protein, and disulfide bond coupling needs to introduce thiol (-SH) structure into protein and polysaccharide, which has many steps.The chemical reagents to be introduced are complex and generally have great toxicity, while the basic requirements of safety and biocompatibility of active substance delivery materials limit their wide use in the field of active substance delivery[31].
Therefore, in this section, Maillard reaction and chemical crosslinking reaction, which are chemical methods with high safety and simple reaction requirements for protein-polysaccharide coupling, are described as follows.

3.2.1.1 Maillard reaction

Maillard reaction is a chemical reaction between protein and reducing sugar on the main chain of polysaccharide, which is a common method to obtain protein polysaccharide crosslinks. As shown in Figure 4, the reaction is carried out under certain conditions of time, temperature, pH and moisture.Because many polysaccharides contain reducing sugars, the electrophilic carbonyl group on the sugar molecule reacts with the neutral amino group on the protein molecule to form a Schiff base, while releasing a molecule of water. Rearrangement of this Schiff base results in the formation of a more stable ketoamine and, consequently, a protein-polysaccharide covalent conjugate[32,33]. Because the Maillard reaction can be initiated under simple conditions without the introduction of other additives, which is very important in the field of food processing, the Maillard reaction has a wide range of practical applications.
Moreover, the Maillard reaction is a viable method for covalent cross-linking of proteins with neutrally charged polysaccharides, such as glucans and starches, where otherwise physical electrostatic complexation of proteins with uncharged polysaccharides is not possible[34,35]. The protein-polysaccharide covalent conjugate with better functional properties can be formed by accurately controlling the Maillard reaction conditions. Zhou et al. Successfully coupled gelatin and neutral charged polysaccharide-dextran by Maillard reaction, encapsulated tea polyphenols, and self-assembled to form complex coacervation core micelles (C3Ms) to achieve efficient delivery of tea polyphenols. MTT assay showed that the toxicity of C3Ms to MCF-7 cells was stronger than that of free tea polyphenols[36].
Martinez-Alvarenga et al. studied the glycosylation degree and color change of maltodextrin-bound whey protein isolate Maillard reaction by various factors, and concluded that temperature and water activity accounted for 48% and 34% of the glycosylation degree and 26% and 46% of the color development, respectively, which were the most important factors affecting the Maillard reaction[37]. Of course, the reaction time is another important factor. Liu et al. Obtained the isolated whey protein-dextran conjugate through Maillard reaction. With the extension of the reaction time, the grafting degree and browning index gradually increased, and the content of α-helix increased from 23.9% to 29.6%.The content of β-sheet and random coil decreased from 23.8% and 38.1% to 19.6% and 32.7%, respectively, and the surface hydrophobicity decreased, while the surface thiol content and total thiol content increased from 5.3 and 15.4 μmol/G to 11.0 and 17.9 μmol/G, respectively[38].
Maillard reaction has attracted much attention because of its simple reaction conditions and no introduction of other chemical reagents. However, Maillard products are usually complex mixtures, and it is difficult to determine their composition and characteristics. Some unwanted advanced glycation end products (AGEs) produced in the later stages of the Maillard reaction can be toxic and may be one of the causative factors of several diseases, therefore, improved control of reaction conditions and thorough product purification are necessary for safe biomedical applications of Maillard products[39]. Methods such as wet heating to shorten the reaction time and the use of antioxidants provide better control of the synthesis process and more possibilities for the Maillard reaction to couple proteins and polysaccharides[40][39].

3.2.1.2 Chemical crosslinking

Chemical cross-linking between proteins and polysaccharides can occur by the addition of a cross-linking agent. However, the release of crosslinking agents into the host due to biodegradation may cause physiological toxicity. For example, glutaraldehyde is a bifunctional aldehyde crosslinker, but it is considered to be a factor that has adverse effects on health, which has led to an increase in the demand for suitable alternative crosslinkers that are low in toxicity, biocompatible, and preferably food grade[17]. The following is a review of the commonly used low-toxicity 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide/n-hydroxysuccinimide (EDC/NHS) coupling, 4- (4,6-dimethoxytriazin-2-yl) -4-methylmorpholine hydrochloride (DMTMM) coupling, and the plant-based crosslinking agent genipin coupling.
EDC/NHS coupling. EDC/NHS is widely used in the induced crosslinking reaction of proteins and polysaccharides because of its non-toxicity and good biocompatibility[41⇓~43]. EDC is a water-soluble, zero-length cross-linker used to couple amine and carboxyl groups, and its cross-linking mode is shown in Fig. 5. EDC can activate the carboxyl group to produce an unstable o-acylisourea as an intermediate, which hydrolyzes and regenerates the carboxyl group when it does not encounter an amine. In the presence of N-hydroxysuccinimide (NHS), EDC can convert the carboxylic acid group into an amine-reactive NHS-ester, which then combines with an amine to form an amide bond[44]. It can be seen that neither EDC nor NHS appears in the final polysaccharide protein conjugate, but only helps the amino and carboxyl groups on the protein and polysaccharide to form amide bonds, and does not become part of the conjugate itself.Instead, it becomes a small molecule by-product that can be washed away by dialysis and other means, which is very popular in the delivery system of active ingredients without introducing other material structures. Maintaining pH control is critical for the EDC/NHS reaction, and relatively low pH values (3.5 to 4.5) are optimal for carboxyl activation by EDC[45].
4- (4,6-Dimethoxytriazin-2-yl) -4-methylmorpholine hydrochloride (DMTMM) is an organic triazine derivative, which can activate the carboxyl group to form an amide. The activation mechanism is similar to the EDC/NHS condensation reaction. DMTMM reacts with the carboxyl group to form a reactive triazine ester intermediate, and then the amino group on the protein and the triazine ester form an amide through bimolecular nucleophilic substitution. The reaction mechanism is shown in Figure 6[46]. Compared with EDC, DMTMM has the advantages of more stability to water, no need to control the pH value for activating carboxyl, easy removal of by-products, and high reactivity[47,48]. In addition, DMTMM-activated carboxylic acids do not readily react with alcoholic hydroxyl groups, so protection of the hydroxyl group is generally not required[49]. At present, DMTMM has systematically studied the crosslinking mechanism, characteristics and applications of carboxyl-containing polysaccharides such as hyaluronic acid, alginate and carboxymethyl cellulose.For example, Golunova et al. Used DMTMM as a crosslinking agent to couple alginate and polypeptide, and proved the effectiveness of DMTMM as a coupling agent to couple the reaction of high molecular weight alginate with molecules of different amino groups[50]. Moreover, DMTMM can be combined with click chemistry to provide a new idea for the combination of polysaccharides, peptides and proteins.
Genipin crosslinking. Genipin is a crosslinking agent of natural origin, which can be prepared by geniposide hydrolysis or microbial transformation, is non-toxic and easily soluble in water, and genipin has been shown to have hepatoprotective activity, as a potent antioxidant and inhibitor of mitochondrial uncoupling protein 2 (UCP2), and has also been reported to have significant anticancer effects[51][52]. Therefore, genipin has significant advantages over the traditional bifunctional crosslinking agent glutaraldehyde. Genipin contains multiple active functional groups such as hydroxyl and carboxyl, and can be monomolecularly or multimolecularly crosslinked with amino-containing polysaccharides and proteins such as gelatin and chitosan. The reaction mechanism of crosslinking is shown in Figure 7[53]. (A) the reaction step is an SN2 nucleophilic substitution reaction, an ester group on a genipin molecule is replaced by a secondary amide bond, (B) the reaction step is that a carbon atom of genipin C3 starts nucleophilic attack from a primary amine group to form an intermediate aldehyde group,After opening of the dihydropyran ring, the secondary amine formed in the first step attacks the resulting aldehyde group, which is then dehydrated and rearranged to form a pyridine-like derivative. (C) shows two ways of crosslinking by genipin, monomolecular genipin bridging and dimeric genipin crosslinking. It can be seen that the crosslinking reactive group of genipin is two amino groups, that is, the crosslinking of amino-containing compounds, such as the crosslinking of chitosan and collagen by genipin, has been widely studied[54]. For the crosslinking between protein and polysaccharide, that is, the crosslinking between amino polysaccharide (such as chitosan) and protein, Mi takes the genipin crosslinking reaction between chitosan and gelatin as an example.The cross-linking process of glycosaminoglycan and protein was demonstrated, and the possibility of fluorescence emission of the conjugate was studied, which provided the possibility of immuno-targeting of therapeutic radionuclides[55].

3.2.2 Enzyme-catalyzed crosslinking

Enzyme-catalyzed cross-linking is also a common way to couple proteins and polysaccharides. Compared with chemical crosslinking methods, enzyme-catalyzed crosslinking has the advantages of short reaction time, mild reaction conditions, high substrate specificity and less by-products, especially in environmental protection and food safety[56]. Proteoglycan coupling reaction mainly uses transglutaminase and a variety of oxidases (mainly tyrosinase, laccase and peroxidase). They have different catalytic cross-linking modes.
The working principle of transglutaminase is to catalyze the acyl transfer of proteins, mainly acting on the acyl transfer reaction between the γ-carboxamide group of glutamine residues and the free amino group. Therefore, a new peptide bond can be formed through it, and the reaction mechanism is shown in Figure 8[57]. In general, the efficiency of the reaction depends on the conformation of the molecule and the abundance and availability of specific amino acid residues in the protein molecule, but this preference for amino groups also limits the method[58]. Yang et al. Used transglutaminase to catalyze the glycosylation reaction of chitooligosaccharide and red bean seed ferritin to prepare chitooligosaccharide-modified ferritin nanoparticles. The glycosylation of chitooligosaccharide maintained the cage-like spherical structure of ferritin.The thermal stability of ferritin was improved, while the reversible assembly of nanoparticles regulated by pH and urea transition was preserved, so that rutin molecules were successfully encapsulated in nanoparticles, which significantly improved the thermal stability of rutin in nanoparticles[59]. It is of great significance for the application of chitosan and transglutaminase in protein modification.
Tyrosinase, laccase, and peroxidase all belong to the family of oxidoreductases and provide broad substrate specificity, catalyzing the oxidation of various compounds with phenol and amine structures. Under their catalysis, reactive tyrosine residues of proteins are oxidized to highly reactive quinone residues.These activated quinone residues can react with nucleophilic substituents (such as chitosan amine groups). The enzymatic oxidation mechanisms of phenols by the three oxidases are different, as shown in Figure 9. Tyrosinase-catalyzed crosslinking is based on quinone generation, while laccase-catalyzed crosslinking is based on free radicals and their further reactions[56,60]. Tyrosine-derived quinones are bound to glucosamine (or chitosan) amine via Schiff base and/or Michel-type addition bonds[61]. Laccase and peroxidase can promote the coupling of proteins containing tyrosine residues with ferulic acid polysaccharides containing phenolic hydroxyl groups (such as arabinoxylan, corn cellulose gum and beet pectin) through free radical reactions. Moreover, laccase-catalyzed oxidation is more environmentally friendly because water is the only by-product, while peroxidase has a broader substrate specificity because peroxidase can catalyze some compounds that laccase cannot, such as monophenols and monoamines[56][60]. Chen et al. Crosslinked gelatin and chitosan with glutamine transaminase and tyrosinase to prepare gels, and compared the properties of the gels prepared by the two schemes.The practical and potential applications of these gels are discussed, and the potential advantages of the enzymatic method are summarized as follows: (I) enzyme-catalyzed gel formation without the introduction of low molecular weight compounds (monomers, initiators, and crosslinkers)[62]. (II) that enzyme directly catalyze the gel formation of polymers without the nee for light or prior grafting of crosslinkable functionality (for example, acrylates are often grafted onto polymer and macromolecules to allow their subsequent gel formation). (III) The gel can be enzymatically synthesized from gelatin and chitosan, two natural polymers with useful functional properties, and the formation of the enzyme-catalyzed gel is simple and mild.
Several covalent or non-covalent binding methods of protein-polysaccharide complex system are introduced above, and mild alkali treatment is also a potential method to prepare protein-polysaccharide complex system. Considering the inherent structure of natural polymers, natural proteins or polysaccharides need to be modified according to the inherent structural characteristics of specific proteins and polysaccharides before application.The newly introduced functional groups may be involved in the complexation of proteins or polysaccharides, and more complex interaction modes provide the possibility for the development of more protein-polysaccharide complex system assembly methods[5]. Table 1 summarizes the main binding modes and influencing factors between protein-polysaccharide complex systems used in active substance delivery systems in current studies.

4 Transport system form of protein-polysaccharide complex system

Protein-polysaccharide complexes can be used as building blocks to create complex structures as delivery vehicles for bioactive components. As shown in Fig. 10, currently reported delivery systems include emulsification systems, micelles, nanogels, molecular complexes, and core-shell structured particles. Hydrophilic (such as epigallocatechin gallate (EGCG), anthocyanin, etc.), hydrophobic (such as curcumin, resveratrol, etc.), active peptides and other bioactive substances can be effectively combined with the protein-polysaccharide complex system to improve the overall efficacy of these bioactive substances. Examples of various delivery systems are shown in Table 2[72⇓⇓~75]. Complex delivery systems can be appropriately designed and constructed according to specific needs, and the following describes the existing common delivery systems.

4.1 Emulsion delivery system

Compared with protein or polysaccharide alone, protein-polysaccharide complex systems can generally improve the stability of the emulsion interface and better protect the bioactive substances in the internal phase of the emulsion. These emulsions are generally divided into nanoemulsions, multiple emulsions and Pickering emulsions.
The protein-polysaccharide complex system can stabilize the emulsion droplets in the nanometer range (50 ~ 1000 nm)[75]. Since the hydrophilic properties of most protein-polysaccharide complex systems exceed their lipophilic properties, protein-polysaccharide complex systems usually form stable oil-in-water emulsions, mainly delivering hydrophobic bioactive substances. Shi et al. Used MRPs, the Maillard reaction products of whey protein isolate and dextran, to prepare O/W emulsion to investigate the protective effect of the emulsion on oil and fat, and proved that the peroxide value (POV) of the oil and fat was reduced from 171.44 meq/kg to 30.63 meq/kg compared with the unmodified protein, which significantly improved the oxidative stability of the emulsion[76]. Multiple emulsions have both water and oil compartments, so they can deliver both hydrophilic and lipophilic bioactive ingredients. The most common multiple emulsion is W/O/W emulsion. The double emulsion stabilized by protein-polysaccharide complex system can improve the loading capacity, chemical stability and controlled release performance of bioactive ingredients[77].
Pickering emulsion is an emulsion stabilized by solid particles. The key factors affecting the performance of Pickering emulsion are the nature of Pickering emulsifier, oil-water ratio, pH value, emulsifier concentration and so on[84]. Protein-polysaccharide particles as Pickering emulsifiers can be assembled using either insoluble (such as gliadins and chitosans) or soluble (such as gelatin and glucomannan) biopolymers. Protein-polysaccharide particle-stabilized Pickering emulsion is a kind of emulsion developed in recent years with the function of delivering bioactive substances because the particles adsorbed on the interface of the emulsion can provide a physical barrier against environmental pressure and have good anti-coalescence stability[85]. Estrada-Fernandez et al. Used whey protein concentrate to interact with gum Arabic to obtain soluble (SC) and insoluble (IC) complexes by adjusting the pH value and material ratio, which were used as oil-in-water and water-in-oil active interfaces, respectively.O1/W/O2 double emulsions were prepared, and the final average particle size changed little after 76 days, indicating that they had long-term stability. The inner oil droplets and double emulsion-like water droplets, as well as the outer Pickering solid particle layer, could be observed by confocal microscopy[79].

4.2 Micelle

Micellar delivery vehicles are spherical supramolecular assemblies of amphiphilic block copolymers. For protein-polysaccharide micelles, amphiphilic block copolymers are mainly Maillard conjugates of protein and polysaccharide, in which the protein and polysaccharide act as hydrophobic head and hydrophilic tail, respectively, and both hydrophobic and hydrophilic bioactive components can be delivered by protein-polysaccharide complex system-based micelles[36]. Li et al. Coupled ovalbumin and dextran through Maillard reaction to form a diblock polymer with ovalbumin as the hydrophobic segment and dextran as the hydrophilic segment, and self-assembled to form nanomicelles with a particle size of 285 ~ 339 nm, which were embedded and delivered to EGCG.The protection of EGCG in the gastrointestinal environment was achieved, and the apparent permeability coefficient (Papp) of EGCG on Caco-2 monolayer was significantly improved by the coupled nanoparticles loaded with EGCG compared with the EGCG solution, indicating that these nanoparticles could improve the absorption of EGCG[74].

4.3 Nanogel

Nanogel carrier has rapidly become one of the main carriers in the field of bioactive substance delivery because of its small particle size, good solubility, high loading and good controlled release[18]. Nanogels are chemically or physically crosslinked by polymers with hydrophilic or amphiphilic macromolecular chains, and have a three-dimensional structure with a particle size in the range of 1200 nm. The structure of nanogels is stabilized by electrostatic interactions, hydrogen bonds, or hydrophobic interactions[86]. Nanogels sequester water molecules in the polymer network in the form of free water or bound water, and the high water content of the internal three-dimensional network supports the flexibility, shrinkage, or expansion of the structure in response to external conditions. This unique structural property makes nanogels often used as nanocarriers to deliver bioactivity into the human system[87]. Natural polysaccharides and proteins are excellent materials for preparing gels, which can be used to prepare nanogels with biocompatibility, biodegradability, low toxicity and low immunogenicity. However, the nanogel system formed by polysaccharide and protein alone is very sensitive, fragile and unstable to the external environment, especially when the polysaccharide alone forms a gel, chemical crosslinking agents are often added[88]. Therefore, in recent years, many studies have widely used various interactions between polysaccharides and proteins to prepare proteoglycan composite nanogel systems. Because of the swelling characteristics of the gel and the structural characteristics of protein and polysaccharide, the protein-polysaccharide composite gel can be designed as a gastrointestinal environment responsive system to achieve the controlled release of active substances and improve the delivery of their bioavailability[89]. Liu et al. Used lysozyme and carboxymethyl cellulose macromolecules to self-assemble and heat to encapsulate tea polyphenols, and formed biodegradable nanogels (Ly-CMC NGs) driven by electrostatic interaction and hydrophobic force. The nanogels were spherical, stable, small in particle size, and high in loading rate (encapsulation rate was 89.05% ± 3.14%).And can realize a compact structure in a gastric acid environment and a loose structure in a small intestine pH environment, so that active substances can be controllably released in the small intestine; the clearance rates of the loaded tea polyphenol nanogel on DPPH and ABTS are 76.5% and 86.1% respectively; and the anti-tumor activity of the loaded tea polyphenol nanogel can effectively inhibit the proliferation of HepG2 cells[90].

4.4 Molecular complex

Molecular complex refers to the molecular assembly formed by the interaction between bioactive substances and biopolymers (proteins or polysaccharides). Polyphenols are the most widely studied bioactive substances in molecular complexes, in which proteins and polysaccharides can be electrostatically assembled or covalently cross-linked, and polyphenols and proteins can be covalently complexed in alkaline solution in the presence of oxygen.Or under the catalysis of oxidases such as laccase and peroxidase, the physical polymer is formed by the combination of quinone and amino groups on proteins, or directly through the interaction force such as hydrogen bonds between hydroxyl groups between polyphenols and proteins[32][91]. Polyphenols and polysaccharides can be covalently bound by free radical grafting initiated by hydroxyl radicals, or polyphenols and polysaccharides containing carboxyl and amino groups (such as chitosan containing amino groups and phenolic acids containing carboxyl groups such as chlorogenic acid and gallic acid) can be induced by EDC/NHS[92]. Because free polyphenols may form insoluble aggregates with biomacromolecules, compared with polyphenol-protein or polyphenol-polysaccharide binary complexes,Polyphenol-protein-polysaccharide ternary molecular complexes can improve the efficacy of polyphenols by improving the physical stability and water solubility of the delivery system, often with superior properties, such as polyphenols usually have strong binding affinity with proteins.This often leads to large-scale aggregation and precipitation. Xia et al. Compared the properties of the molecular complex of bovine serum albumin and EGCG before and after the introduction of dextran Maillard glycosylation.It was found that the hydrophilic layer of dextran inhibited the strong interaction between bovine serum albumin and EGCG, which was dominated by hydrophobic interaction and hydrogen bonding, and finally inhibited the large-scale aggregation[93].
In addition, the polyphenol-protein-polysaccharide ternary molecular complex can improve the functionality of the protein-polysaccharide complex, such as the advantages of polyphenol in anti-oxidation and anti-free radical,Liu et al. Obtained the covalent complex of chlorogenic acid and lactoferrin by alkaline oxidation, and then glycosylated it with dextran by Maillard reaction to prepare the ternary covalent complex of chlorogenic acid-lactoferrin/dextran[94]. The complex effectively improves the hydrophilicity of the surface of the β-carotene emulsion, enhances the space repulsion between oil droplets, improves the physical and chemical stability of the emulsion, and significantly improves the anti-ultraviolet stability of β-carotene in the emulsion[95]. Furthermore, the effect of the interfacial coating composed of the chlorogenic acid-lactoferrin/dextran ternary covalent complex on the performance of β-carotene lipid droplets during digestion was studied.Emulsion stabilized by this ternary conjugated system was more stable to droplet aggregation than other systems under simulated gastrointestinal conditions, improving the bioaccessibility of β-carotene[96].

4.5 Shell-core structured particle

Core-shell particles are often used for the delivery of hydrophobic bioactive components. Generally speaking, hydrophobic proteins (corn protein, soybean protein, etc.) Are first assembled into protein particles as the inner core, and then the bioactive components are encapsulated into the inner core mainly through hydrophobic interaction, and the hydrophilic polysaccharides are attached to the nuclear sphere in the form of shells. The pyrenoid promotes encapsulation and protection of hydrophobic bioactive components, and the polysaccharide shell improves particle stability by creating stronger steric and electrostatic repulsion[97]. Huang et al. Prepared core-shell nanoparticles composed of hydrophobic corn protein core coated with hydrophilic pectin shell by electrostatic deposition method to encapsulate curcumin, which has the characteristics of high curcumin loading efficiency, high particle yield and good water dispersibility, and tried to replace 30% of pectin with alginate.The aggregation stability of the particles was greatly improved, and curcumin showed higher antioxidant and radical scavenging activities after coating these core-shell nanoparticles, as analyzed by Fe (Ⅲ) reducing power, DPPH · radical and ABTS·+ radical cation scavenging experiments[2]. They continued to develop core-shell nanoparticles of hydrophobic zein-pectin prepared by anti-solvent precipitation method to encapsulate resveratrol, which showed good in vitro antioxidant and anticancer properties[72]. In recent years, new materials have been developed, such as hordein and EGCG, which were successfully prepared into nanoparticle cores by anti-solvent liquid-liquid dispersion method, and then coated with chitosan shell by electrostatic layer-by-layer stacking method.Cs-EHNs with core-shell structure were formed, and the effect of chitosan shell on the absorption and transcellular permeability of Cs-EHNs was studied by Caco-2/HT29 cell co-culture model[22]. Cs-EHNs could significantly increase the transcellular permeability of EGCG, and the apparent permeability coefficient (Papp) of Cs-EHNs was higher than that of free EGCG. In addition, the cellular uptake of Cs-EHNs was studied by specific endocytosis inhibitors, and the results showed that the uptake mechanism of Cs-EHNs was vesicle-mediated endocytosis and macropinocytosis. The schematic diagram of the preparation process and the absorption effect of EGCG are shown in Figure 11.

5 Development Trend of Intelligence and Targeting

In the field of pharmaceutical preparations, the difference of pH value and enzyme environment of gastrointestinal tract environment, the difference of pH value, oxidation-reduction environment and temperature of lesion site, and the high concentration of glucose in the blood of hyperglycemic patients are utilized.A variety of pH-responsive, reduction-responsive, temperature-responsive, glucose-responsive and receptor-targeted drug entrapment delivery systems have been designed. Inspired by this idea, this development direction has become a trend in the delivery of bioactive substances[98⇓~100][1,101]. The structure of some polysaccharides or proteins is environmentally sensitive, for example, the primary amino groups on chitosan allow chitosan to dissolve at low pH and shrink and aggregate at high pH, which is a good targeted controlled release material for the weak acid microenvironment of cancer cells. Polymers containing carboxyl groups, such as sodium alginate, pectin and hyaluronic acid, on the contrary, can contract and protect active substances under acidic conditions of gastric juice, and swell and release in near-neutral environment of intestinal tract to achieve high transmission efficiency and bioavailability[11]. In recent years, the chemical modification of natural proteins and polysaccharide polymers to graft environmentally sensitive groups has also become one of the research hotspots. Huang et al. Used the —NH2 on bovine serum albumin (BSA) as the target modification group, and coupled it with PNIPAAm polymer activated by mercaptothiazoline.Protein-polymer conjugate (BSA-NH2/PNIPAAm) with thermal sensitivity response was prepared, and then the vesicle structure was formed by Pickering emulsification, which not only provided the ability to produce target microcontainers,It also provides the ability to release bioactive substance load mediated by temperature, and provides a scheme for the construction of targeted delivery multifunctional microchambers with high biocompatibility and cell recognition level[102]. The preparation scheme and thermal response behavior of the thermosensitive conjugate and emulsion are shown in Figure 12.
On the other hand, considering the convenience of oral administration and the improvement of bioavailability, transporters designed by using various specific receptors and transporters highly expressed by intestinal epithelial cells for active transport have also received great attention, such as folate receptor, vitamin B12 receptor, transferrin receptor and bile acid transporter[103]. Fan et al. Self-assembled chitosan with γ-polyglutamic acid and insulin, a model compound of polypeptide active substances, through non-covalent physical copolymerization.The formed insulin-loaded deoxycholic acid targeting modified nanoparticles (DNPs) can overcome the multiple barriers of intestinal epithelium through the bile acid pathway, realize the protection of insulin in the harsh pH and enzyme environment of the gastrointestinal tract,At the same time, during the operation of intestinal epithelial cells, it is internalized by endocytosis mediated by apical sodium-dependent bile acid transporter (ASBT), and lysosomal escape significantly prevents insulin degradation in epithelial cells. The oral bioavailability of type I diabetic rats is 15.9%, which provides a delivery scheme for the oral absorption of polypeptide active substances[104]. Fig. 13 shows the construction scheme of the targeted DNPs nanoparticles, the uptake mechanism by epithelial cells, and the bile acid pathway transport from DNPs across epithelial cells to overcome the multiple barriers of intestinal epithelial cells. In addition, the construction and research of fatty acid-specific intestinal cell transporters, such as fatty acid transporter 4 (FATP4) and monocarboxylate transporter 1 (MCT1) targeted transporters, is also a very meaningful development direction for the transmission of active substances[105,106].

6 Conclusion and prospect

Since the pioneering work of de Jong et al. On complex coacervation of gelatin-gum Arabic system (a protein-polysaccharide system), polysaccharide and protein complexes have received more and more attention in practical applications.Because it has multiple significant advantages in the delivery of bioactive substances: (I) high biosafety and biocompatibility of protein and polysaccharide materials. (II) There are many kinds of proteins and polysaccharides, and many of them contain excellent modifiable active groups such as amino, carboxyl, hydroxyl, amide, phenol and other structures, which make the relationship between proteins and polysaccharides.The protein-polysaccharide complex system can be formed by safe and effective methods such as physical non-covalent complex, Maillard reaction, EDC/NHS crosslinking, enzyme crosslinking and the like with few by-products or even no by-products. (III) The protein-polysaccharide complex system can be formed in various forms for encapsulating active substances, and the required protein and polysaccharide materials and the required delivery forms can be selected according to the different delivery requirements of different active substances, such as solubilization, anti-oxidation, gastrointestinal pH and enzyme environmental protection, overcoming adsorption barriers to improve bioavailability, etc.
However, although the assembly of protein-polysaccharide complex systems facilitates the delivery of bioactive substances in many ways, the design, evaluation, and application of delivery systems still face many challenges. The overall efficiency of protein-polysaccharide complex systems in the delivery of bioactive components needs to be reconsidered and improved. First of all, in order to achieve the best transfer performance, appropriate proteins and polysaccharides should be selected as wall materials according to the specific needs of bioactivity transfer, which requires a full and comprehensive understanding of the structure of a variety of proteins and polysaccharides. For example, proteins with hydrophobic holes are more suitable for the delivery of hydrophobic bioactive compounds; In order to improve the intestinal permeability of bioactive substances, it may be a good choice to design composite nanoparticles with chitosan as the outer layer, because chitosan is easier to adhere to and penetrate into the mucus layer than other polysaccharides. If we want to design a pH-responsive delivery system to protect active substances in gastric juice and release active substances in the intestine, polysaccharides naturally containing — COOH, such as sodium alginate, pectin and other polysaccharides, may be very conducive to the realization of the goal. Secondly, after the construction of the delivery system of the protein-polysaccharide complex system, most of the in vitro digestion models currently used to evaluate the bioaccessibility of bioactive ingredients are static systems based on the "beaker test", without considering practical factors such as intestinal peristalsis and dynamic changes. In addition, in the intelligent and targeted modification of protein-polysaccharide complex system, most of the current modifications may still introduce more chemical substances, which is different from the goal of high biosafety of protein-polysaccharide complex system to deliver bioactive substances, and more safe and efficient preparation schemes need to be developed. Alternatively, to date, in vivo pharmacokinetic studies on how proteins or polysaccharides affect the bioavailability of bioactive components, as well as mechanistic studies on cellular uptake, particularly at the subcellular structural level, are still very limited.
To sum up, the protein-polysaccharide complex system is a promising carrier for the encapsulation and delivery of active ingredients, and we can design the delivery system of active ingredients safely, reasonably and effectively on the basis of a more comprehensive and in-depth understanding of its impact on active ingredients and efficacy.

References

Publishing order | Descend order by publishing year | Descend order by cited within
[1]

Nowak E, Livney Y D, Niu Z, Singh H. Trends in Food Science & Technology, 2019, 91: 557.
[2]

Huang X X, Huang X L, Gong Y S, Xiao H, McClements D J, Hu K. Food Res. Int., 2016, 87: 1.
[3]

Thongkaew C, Gibis M, Hinrichs J, Weiss J. Food Hydrocolloids, 2014, 41: 103.
[4]

Shaddel R, Hesari J, Azadmard-Damirchi S, Hamishehkar H, Fathi-Achachlouei B, Huang Q. Food Hydrocolloids, 2018, 77: 803.
[5]

Wei Z, Yang W, Fan R, Yuan F, Gao Y. Food Hydrocolloids, 2015, 45: 337.
[6]

Troszynska A, Narolewska O, Robredo S, Estrella I, Hernandez T, Lamparski G, Amarowicz R. Food Quality and Preference, 2010, 21 (5): 463.
[7]

Ting Y, Jiang Y, Zhao S, Li C C, Nibber T, Huang Q. Journal of Functional Foods, 2018, 40: 520.
[8]

Chen G, Roy I, Yang C, Prasad P N. Chem Rev, 2016, 116 (5): 2826.
[9]

Zhao Y, Cao W Q, Liu Y. Chemical Research in Chinese Universitie, 2020, 41 (5): 909.
[10]

赵宇, 曹琬晴, 刘阳. 高等学校化学学报, 2020, 41 (5): 909.).
[11]

Fonte P, Araujo F, Silva C, Pereira C, Reis S, Santos H A, Sarmento B. Biotechnol Adv, 2015, 33 (6 Pt 3): 1342.
[12]

Nur M, Vasiljevic T. Int J Biol. Macromol., 2017, 103: 889.
[13]

Wang S Y, Feng Y M, Wu J L, Chen X, Feng J W, Shi X D, Cai X X, Zhang F. Food Sci., 2021, 42(17): 1.
[14]

汪少芸, 冯雅梅, 伍久林, 陈旭, 冯佳雯, 施晓丹, 蔡茜茜, 张芳. 食品科学, 2021, 42(17): 1. ).
[15]

Beneke C E, Viljoen A M, Hamman J H. Molecules, 2009, 14 (7): 2602.
[16]

Cortes-Morales E A, Mendez-Montealvo G, Velazquez G. Adv Colloid Interface Sci, 2021, 295: 102398.
[17]

Feki A, Hamdi M, Jaballi I, Zghal S, Nasri M, Ben Amara I. Carbohydr Polym, 2020, 236: 116046.
[18]

Devi N, Sarmah M, Khatun B, Maji T K. Adv. Colloid Interface Sci., 2017, 239: 136.
[19]

Wei Z H, Huang Q R. J. Agric. Food Chem., 2019, 67(5): 1344.
[20]

Zhang Z, Hao G, Liu C, Fu J, Hu D, Rong J, Yang X. Food Res. Int., 2021, 147: 110564.
[21]

Laplante S, Turgeon S L, Paquin P. Carbohydrate Polymers, 2006, 65 (4): 479.
[22]

Chen Y Q, Song H D, Huang K, Guan X. Food Funct., 2021, 12(19): 9165.
[23]

Tiebackx F W. Colloid and Polymer Science, 1911, 8 (4): 198.
[24]

Song H D, He A J, Guan X, Chen Z Y, Bao Y Z, Huang K. Int. J. Biol. Macromol., 2022, 196: 144.
[25]

Ji N. Doctoral Dissertation of Jiangnan University, 2019.
[26]

姬娜. 江南大学博士论文, 2019.).
[27]

Lim H P, Ooi C W, Tey B T, Chan eng-seng. React. Funct. Polym., 2017, 120: 20.
[28]

Lu M L, Li Z J, Liang H, Shi M X, Zhao L H, Li W, Chen Y Y, Wu J D, Wang S S, Chen X D, Yuan Q P, Li Y. Food Hydrocoll., 2015, 51: 476.
[29]

Ru Q M, Wang Y W, Lee J, Ding Y T, Huang Q R. Carbohydr. Polym., 2012, 88(3): 838.
[30]

Hu B, Wang S S, Li J, Zeng X X, Huang Q R. J. Phys. Chem. B, 2011, 115(23): 7515.
[31]

Weinbreck F, de Vries R, Schrooyen P, de Kruif C G. Biomacromolecules, 2003, 4(2): 293.
[32]

Eghbal N, Choudhary R. LWT, 2018, 90: 254.
[33]

Chen C, Chen F S, Liu B Y. The Food Industry, 2019, 40 (2): 225.
[34]

陈晨, 陈复生, 刘伯业. 食品工业, 2019, 40 (2): 225.).
[35]

Zhou Y, Petrova S P, Edgar K J. Carbohydr. Polym., 2021, 274: 118662.
[36]

Liu F G. Doctoral Dissertation of China Agricultural University, 2017.
[37]

刘夫国. 中国农业大学博士论文, 2017.).
[38]

Aoki T, Iskandar S, Yoshida T, Takahashi K, Hattori M. Biosci. Biotechnol. Biochem., 2006, 70(10): 2349.
[39]

Consoli L, Dias R A O, Rabelo R S, Furtado G F, Sussulini A, Cunha R L, Hubinger M D. Food Hydrocoll., 2018, 84: 458.
[40]

Liu Q, Li M, Xiong L, Qiu L Z, Bian X L, Sun C R, Sun Q J. Food Hydrocoll., 2019, 92: 86.
[41]

Zhou H H, Sun X Y, Zhang L L, Zhang P, Li J, Liu Y N. Langmuir, 2012, 28(41): 14553.
[42]

Martinez-Alvarenga M S, Martinez-Rodriguez E Y, Garcia-Amezquita L E, Olivas G I, Zamudio-Flores P B, Acosta-Muniz C H, Sepulveda D R. Food Hydrocoll., 2014, 38: 110.
[43]

Liu Q, Cui H, Muhoza B, Hayat K, Hussain S, Tahir M U, Zhang X, Ho C T. LWT, 2021, 148.
[44]

Silvan J M, Assar S H, Srey C, Dolores Del Castillo M, Ames J M. Food Chem., 2011, 128 (1): 208.
[45]

Zhu D, Damodaran S, Lucey J A. Journal of Agricultural and Food Chemistry, 2008, 56 (16): 7113.
[46]

Wang D, Mao L, Dai L, Yuan F, Gao Y. Food Hydrocolloids, 2018, 80: 281.
[47]

Kaczmarek B, Sionkowska A, Kozlowska J, Osyczka A M. Int. J. Biol. Macromol., 2018, 107 (Pt A): 247.
[48]

Goodarzi H, Jadidi K, Pourmotabed S, Sharifi E, Aghamollaei H. Int. J. Biol. Macromol., 2019, 126: 620.
[49]

Bart J, Tiggelaar R, Yang M, Schlautmann S, Zuilhof H, Gardeniers H. Lab Chip, 2009, 9 (24): 3481.
[50]

Nakajima N, Ikada Y. Bioconjugate Chem., 1995, 6(1): 123.
[51]

D’Este M, Eglin D, Alini M. Carbohydr. Polym., 2014, 108: 239.
[52]

Farkas P, Bystricky S. Carbohydrate Polymers, 2007, 68 (1): 187.
[53]

Farkas P, Cizova A, Bekesova S, Bystricky S. Int. J. Biol. Macromol., 2013, 60: 325.
[54]

Labre F, Mathieu S, Chaud P, Morvan P Y, VallÉe R, Helbert W, Fort S. Carbohydr. Polym., 2018, 184: 427.
[55]

Golunova A, Velychkivska N, Miksovska Z, Chochola V, Jaros J, Hampl A, Pop-Georgievski O, Proks V. Int. J. Mol. Sci., 2021, 22 (11).
[56]

Zhang C, Wang P, Li J, Zhang H, Weiss J. Food Hydrocolloids, 2021, 119.
[57]

Shanmugam M K, Shen H Y, Tang F R, Arfuso F, Rajesh M, Wang L Z, Kumar A P, Bian J S, Goh B C, Bishayee A, Sethi G. Pharmacol. Res., 2018, 133: 195.
[58]

Butler M F, Ng Y F, Pudney P D A. J. Polym. Sci. A Polym. Chem., 2003, 41(24): 3941.
[59]

Adamiak K, Sionkowska A. Int. J. Biol. Macromol., 2020, 161: 550.
[60]

Mi F L. Biomacromolecules, 2005, 6(2): 975.
[61]

Wu T, Liu C, Hu X. Food Chem., 2022, 372: 131332.
[62]

Buchert J, Ercili Cura D, Ma H R, Gasparetti C, Monogioudi E, Faccio G, Mattinen M, Boer H, Partanen R, Selinheimo E, Lantto R, Kruus K. Annu. Rev. Food Sci. Technol., 2010, 1: 113.
[63]

Isaschar-Ovdat S, Fishman A. Trends Food Sci. Technol., 2018, 72: 134.
[64]

Yang R, Zuo P, Zhang M, Meng D M, Wang B W, Zhen T Y. Food Hydrocoll., 2019, 94: 500.
[65]

Li X Q, Li S Q, Liang X P, McClements D J, Liu X B, Liu F G. Trends Food Sci. Technol., 2020, 103: 78.
[66]

Chen T H, Small D A, Wu L Q, Rubloff G W, Ghodssi R, Vazquez-Duhalt R, Bentley W E, Payne G F. Langmuir, 2003, 19(22): 9382.
[67]

Chen T H, Embree H D, Brown E M, Taylor M M, Payne G F. Biomaterials, 2003, 24(17): 2831.
[68]

Zhang Q, Jeganathan B, Dong H M, Chen L Y, Vasanthan T. Food Chem., 2021, 344: 128569.
[69]

Jiang L, Ren Y M, Xiao Y H, Liu S S, Zhang J H, Yu Q, Chen Y, Xie J H. Carbohydr. Polym., 2020, 242: 116424.
[70]

Wang L, Cao Y P, Zhang K, Fang Y P, Nishinari K, Phillips G O. Colloids Surf. A Physicochem. Eng. Aspects, 2015, 482: 604.
[71]

Xiong W F, Deng Q C, Li J, Li B, Zhong Q X. Food Hydrocoll., 2020, 98: 105282.
[72]

Ghaedi N, Hosseini E. LWT, 2021, 152: 112352.
[73]

Lin J W, Meng H C, Yu S J, Wang Z M, Ai C, Zhang T, Guo X M. Food Hydrocoll., 2021, 112: 106306.
[74]

Choi Y R, Kim E H, Lim S, Choi Y S. Biochem. Eng. J., 2018, 129: 50.
[75]

Li J L, Cheng Y Q, Wang P, Zhao W T, Yin L J, Saito M. Food Hydrocoll., 2012, 26(2): 448.
[76]

Wang D, Lv P F, Zhang L, Yang S Q, Gao Y X. J. Agric. Food Chem., 2019, 67(43): 12054.
[77]

Huang X L, Dai Y Q, Cai J X, Zhong N J, Xiao H, McClements D J, Hu K. Food Hydrocoll., 2017, 64: 157.
[78]

Feng J, Wu S S, Wang H, Liu S B. J. Funct. Foods, 2016, 27: 55.
[79]

Li Z, Gu L W. J. Agric. Food Chem., 2014, 62(6): 1301.
[80]

Zeng T, Wu Z L, Zhu J Y, Yin S W, Tang C H, Wu L Y, Yang X Q. Food Chem., 2017, 231: 122.
[81]

Shi Y Q, Liang R, Chen L, Liu H, Goff H D, Ma J G, Zhong F. Food Hydrocoll., 2019, 87: 582.
[82]

Faridi Esfanjani A, Jafari S M, Assadpour E. Food Chem., 2017, 221: 1962.
[83]

Liu F, Liang X, Yan J, Zhao S, Li S, Liu X, Ngai T, McClements D J. Biomaterials, 2022, 280: 121265.
[84]

Estrada-Fernández A G, Román-Guerrero A, JimÉnez-Alvarado R, Lobato-Calleros C, Alvarez-Ramirez J, Vernon-Carter E J. J. Food Eng., 2018, 221: 35.
[85]

Li M, Wen X, Wang K L, Liu Z H, Ni Y Y. Food Chem., 2022, 387: 132914.
[86]

Zeng Q, Zeng W, Jin Y, Sheng L. Food Chem., 2022, 367: 130716.
[87]

Muhoza B, Xia S, Cai J, Zhang X, Duhoranimana E, Su J. Food Hydrocolloids, 2019, 87: 712.
[88]

Wu D, Tang L, Zeng Z, Zhang J, Hu X, Pan Q, Geng F, Li H. Food Chem., 2022, 386: 132837.
[89]

Tian S W, Mao G L, Zhang J Y, Li N, Jiang M Y, Wu W. Prog. Chem., 2020, 32(4): 434.
[90]

田诗伟, 毛国梁, 张珈瑜, 历娜, 姜梦圆, 吴韦. 化学进展, 2020, 32(4): 434. ).
[91]

Wei Z H, Huang Q R. Food Hydrocoll., 2019, 89: 590.
[92]

Neamtu I, Rusu A G, Diaconu A, Nita L E, Chiriac A P. Drug Deliv., 2017, 24(1): 539.
[93]

Yu Q L, Li Z, Dou C Y, Zhao Y P, Gong J X, Zhang J F. Prog. Chem., 2020, 32(S1): 179.
[94]

于秋灵, 李政, 窦春妍, 赵义平, 巩继贤, 张健飞. 化学进展, 2020, 32(S1): 179. ).
[95]

Papagiannopoulos A, Vlassi E, Radulescu A. Carbohydr. Polym., 2019, 218: 218.
[96]

Tai M R, Cai H Y, Li R, Chen J P, Jia X J, Song B B, Liu X F, Tang Z D, Ji H W, Zhong S Y. Food and Fermentation Industries. 2022, 48 (3): 291.
[97]

太敏瑞, 蔡泓滢, 李瑞, 陈建平, 贾学静, 宋兵兵, 刘晓菲, 唐振冬, 吉宏武, 钟赛意. 食品与发酵工业, 2022, 48 (3): 291.).
[98]

Liu C, Zhang Z, Kong Q J, Zhang R G, Yang X B. RSC Adv., 2019, 9(18): 10004.
[99]

Chen Y C, Yu S H, Tsai G J, Tang D W, Mi F L, Peng Y P. J. Agric. Food Chem., 2010, 58(11): 6728.
[100]

Wei Z H, Gao Y X. LWT Food Sci. Technol., 2016, 71: 295.
[101]

Xia S Q, Li Y Q, Xia Q Y, Zhang X M, Huang Q R. Food Hydrocoll., 2015, 43: 228.
[102]

Liu F G, Sun C X, Wang D, Yuan F, Gao Y X. RSC Adv., 2015, 5(95): 78215.
[103]

Liu F G, Wang D, Xu H G, Sun C X, Gao Y X. Food Chem., 2016, 196: 338.
[104]

Liu F G, Ma C C, Zhang R J, Gao Y X, Julian McClements D. Food Chem., 2017, 221: 395.
[105]

Chen F P, Ou S Y, Tang C H. J. Agric. Food Chem., 2016, 64(24): 5053.
[106]

Hu X L, Zhang Y Q, Xie Z G, Jing X B, Bellotti A, Gu Z. Biomacromolecules, 2017, 18(3): 649.
[107]

Wang X H, Wang X Y, Jin S X, Muhammad N, Guo Z J. Chem. Rev., 2019, 119(2): 1138.
[108]

Jing X D, Sun Y, Yu B, Shen Y Q, Hu H, Cong H L. Progress in Chemistry, 2021, 33 (6): 926.
[109]

荆晓东, 孙莹, 于冰, 申有青, 胡浩, 丛海林. 化学进展, 2021, 33 (6): 926.).
[110]

Li S, Lv H Y, Chen Y, Song H D, Zhang Y, Wang S, Luo L, Guan X. Carbohydr. Polym., 2022, 286: 119273.
[111]

Huang X, Li M, Green D C, Williams D S, Patil A J, Mann S. Nat. Commun., 2013, 4: 2239.
[112]

Fan W W. Doctoral Dissertation of University of Chinese Academy of Sciences, 2019.
[113]

范卫伟. 中国科学院大学博士论文, 2019.).
[114]

Fan W W, Xia D N, Zhu Q L, Li X Y, He S F, Zhu C L, Guo S Y, Hovgaard L, Yang M S, Gan Y. Biomaterials, 2018, 151: 13.
[115]

Nizzero S, Goel S, Hinkle L E, Wu X Y, Li C, Ferrari M, Shen H F. Sci. Adv., 2020, 6(26): eaba0145.
[116]

Wang G, Zhao L C, jiang Q K, Sun Y X, Zhao D Y, Sun M C, He Z G, sun J, Wang Y. Asian J. Pharm. Sci., 2020, 15(2): 158.

Funding

National Natural Science Foundation of China(32172247)

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