Pectin-based Encapsulation Systems for Bioactive Components

Abstract

Pectin is a soluble dietary fiber with several health benefits, such as antibacterial, antioxidant, gastrointestinal-protective, and anticancer properties. Pectin is becoming an important class of materials owing to their inherent structural and functional properties such as biodegradability, binding potential, self-assembly, high nutritional value, gelling properties, non-toxicity, and good biocompatibility. Pectin is highly beneficial in microencapsulation since it allows for better control over the toxicity of the active substances and ensures the safety of the customer. Pectin offers a safe route for drug delivery due to its well-designed molecular architecture based on the changes in the biological process’s fundamental mechanisms. The current arising insight into the chemical structure and associated health advantages of pectin opens new opportunities for the use of pectin in nutraceutical encapsulation and drug delivery. Pectin can be obtained from various plant sources at a lower cost. Thus, pectin is a promising biopolymer when designing materials that may achieve the highly desired dual objectives of being environmentally friendly and economically sustainable. This chapter emphasizes pectin-based nano and microencapsulation systems, their tailor-made functionalities, and their applications in the pharmaceutical and food industry.

1. Introduction

The use of stable and active ingredients has taken center stage in both food and pharmaceutical industries as a result of the growing and expanding global knowledge of the value of a nutritious diet and its effect on preventing illness. Additionally, an increasing trend among consumers is their preference for foods made with natural ingredients. Many of such active ingredients lose their health benefits when it is added to a food matrix. One method for preserving the efficacy of food ingredients and promoting the creation of novel, nutritionally sound foods is the microencapsulation of these active food components [1]. The major active substances that encapsulate are essential oils, probiotics, minerals, vitamins, bioactive lipids, antioxidants, and enzymes [2]. Encapsulating substances to preserve flavor or prevent undesirable organoleptic qualities without sacrificing functionality is a commonly cited rationale.

Certain polymers have been used for encapsulation to preserve all of the functionality of the food components. Researchers are mostly focusing on microencapsulation methods using natural polymers. Because it is safer as well and consumers prefer products that use natural polymers. These polymers must satisfy regulatory standards, which can differ by nation and physicochemical requirements. Polymers used for microencapsulation generally need to have certain qualities; that is, the polymers used must be able to preserve all the properties of encapsulated active ingredients under elevated environmental conditions. However, when needed for the application, it should release the cargo, at right time and location [3]. Not to mention, it ought to be affordable and food-grade.

Proteins and carbohydrates are the main kinds of natural polymers that are most frequently used to encapsulate food. Each of these materials has benefits and drawbacks depending on the use. Certain components provide challenges when integrating them into the food matrix, while others may be expensive for numerous uses [4].

Pectin, a ubiquitous natural biomaterial, due to its unique advantages, has received particular attention in recent years when it comes to the encapsulation of food ingredients. Pectins are high molecular weight anionic heteropolysaccharides that, generally non-hazardous in nature, can form microencapsulation systems around active ingredients. As an encapsulating polymer, pectin offers many advantages. Pectin provides health advantages in addition to being useful for controlling and delivering active ingredients precisely to certain parts of the digestive tract. Pectin has the ability to stop gastrointestinal tract inflammation and may even stop some major illnesses, as this chapter will detail. These beneficial properties of pectin make it a promising polymer in the microencapsulation research area [5]. On the other hand, debates about the benefits and limitations of using pectin in food, as well as the kind of pectin that should be used in microencapsulation systems, are continuing. The potential of pectin to encapsulate particular food and pharmaceutical ingredients has been taken into consideration when writing the current book chapter.

2. Sources of pectin

Pectin is a polysaccharide present in plant cell walls that plays a role in intricate physiological processes like cell division and cell growth, which in turn affect the integrity and firmness of plant tissue. As a component of the cell wall, pectin is essential for giving plants structural support. The primary cell wall has a highly concentrated crosslinked network of cellulose and hemicelluloses, but pectin plays a crucial function in binding this network together [6]. According to structural research, pectin functions as a matrix into which the fibrils of cellulose and hemicellulose are inserted and fused to form a structural unit. Pectin is abundant in the middle lamella, and they are essential for the development of cell–cell adhesion in a variety of plant tissues [6].

Additionally, they are crucial to the defense systems against wounds and plant infections. Owing to their anionic characteristics, pectic polysaccharides are thought to have a role in regulating ion transport, wall porosity, and, consequently, the permeability of the walls for enzymes. They ascertain the water-holding capacity as well [7]. Fresh and processed food product’s quality criteria are significantly influenced by the quantity and composition of pectin polymers found in fruits, vegetables, and other plant products.

It is possible to extract pectin from appropriate agricultural byproducts utilized in the food sector. Pectin is mostly produced commercially from apple pomace and citrus peels [8]. The pectin content in citrus peel is thought to be between 25 and 30 percent dry weight [9], compared to 10 to 15 percent in apple pomace. Pectin can also be extracted from other waste byproducts from industries, such as cocoa pod husks, grapefruit peels, pomegranate peels, passion fruit peels, mango peels, banana peels, kiwi fruit pomace, pistachio green hulls, tomato waste, sugar beet, sunflower head, pumpkin, watermelon rind, and potato pulp [10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23]. The need for the exploration of alternative pectin sources has arisen from the quick rise in demand for pectin owing to its extensive uses in various industries.

3. Physicochemical properties of pectin

Pectin is a complex heteropolysaccharide with significant intra- and intermolecular variability. Pectin is made up of segments of a long galacturonan chain as well as additional neutral sugars like rhamnose, xylose, galactose, and arabinose. Together with celluloses and hemicelluloses, it creates a matrix that supports cell structure.

According to a structural study, pectin is a polymer with a chain-like arrangement made up of between 100 and 1000 saccharide units; as a result, it lacks a clearly defined structure. Pectin is commonly represented as a heteropolysaccharide consisting of mainly three constituents: homogalacturonan (HG), rhamnogalacturonan I (RG-I), and rhamnogalacturonan II (RG-II). The other neutral sugar units including xylogalacturonan (XG), Arabinan, arabinogalactan I (AG-I), and arabinogalactan II (AG-II) may branch with the backbone structure. Around 60% of all the pectins in cell walls are homogalactalacturonan, a simple, non-substituted chain of polygalacturonic acid known as “smooth” chains. The structural description of Rhamnogalacturonan I (RG-I) is a lengthy backbone sequence of alternating α-(1 → 4) linked galacturonic acid (GalA) units and α-(1 → 2) linked D-rhamnose, consisting of spatially organized polymers. It may get O-acetylated at the GalA residues’ O-2 or O-3 sites. Whereas rhamnogalacturonan II is made up of a homogalacturonan backbone switched with a wide range of complex side chains of glycan, comprising several types of neutral sugars, GalA, which is found in the (RG-II) backbone, might be methyl esterified at C-6 position. Xylogalacturonan (XG) is made up of the α-(1–4) linked D-GalA in the backbone linked by xylose in branches. The α-(1–4) glycosidic linkages are present throughout the homogalacturonan pectin chains. Depending on the pectin source, the amount of GalA residues in HG can range from 72 to 100%. Moreover, it was noted that HG might be O-acetylated at the O-2 and/or O-3 and/or methoxy-esterified at the C-6. HG can be degraded and de-esterified by both enzymatic and mechanical means. Galactan and arabinan polymeric side chains are substituted at the RG-I backbone’s O-4 position. It has also been observed that Arabinogalactan I (AG-I) and Arabinogalactan II (AG-II) exist as polymeric side chains. The side chains, often known as “hairs,” are thought to be crucial to the functioning of pectin. The solubility of the pectin may increase as a result of side chain loss [24].

Pectin molecules have a certain degree of methyl-esterification and acetylation on the galacturonic acid units. For the time of the esterification reaction of pectin, the hydrogen on the carboxylic acid group is changed to a methyl group (CH₃), transforming the R group from COOH to COOCH₃. The degree of esterification of D-galacturonic acid refers to the proportion of its carboxyl groups that have undergone methyl group esterification. The esterification of the galacturonic acid groups with methyl groups at C-6 and acetyl groups at O-2 and O-3 on the homogalacturonan is the basis for the specific structural arrangement of pectin [24].

The pectin charge is mainly determined by the presence and distribution of esterified and nonesterified galacturonic acids. Pectins are classified as high-methoxy pectin (HMP) or low-methoxy pectin (LMP) based on their degree of esterification (DE). The degree of esterification is less than 50% in LMP, whereas HMP pectin has DE values above 50% [25]. Besides, it was ascertained that the viscosity, solubility, and gelation characteristics of pectin are strongly correlated with structural characteristics [24].

4. Pectin as a functional biomaterial

Pectin is a weak acid, that contains carboxyl, hydroxyl, acetyl, and ester functional groups for chemical response. It has a pKa range of 2.9–5.4. The functional hydroxyl groups at C2 or those at C6 located in the equatorial site of pectin are chemically more reactive. Pectin’s interactions with various small and macromolecules, as well as with each other, are determined by its structural and molecular properties. Pectin can help to remove toxic heavy metals such as mercury, lead, arsenic and cadmium through the mechanism of metal chelation. Pectin binds to these toxic metals and forms complex structures that are able to be removed from the body through excretion. Pectin with a lower degree of esterification is rich in free carboxyl groups, which is ideal for the chelation of cations or metals [26].

The pH of the stomach is 2 or below. In this stomach environment, the carboxyl groups in pectin become protonated. As a result, there is less pectin-cation binding and a greater cation release. In the small intestine (pH 6-7), pectin is highly charged due to the ionization of carboxyl groups at higher pH. This will promote the electrostatic interaction between pectin and cations [26]. In the colon or large intestine, there are microflora that can ferment pectin, thereby increasing the release of bound divalent cations. Thereby increasing the potential for cation absorption [27]. The high viscosities and high molecular weight of pectin can help to function as a natural barrier around the oxidative enzymes and can suppress the actions [28]. The carboxyl and hydroxyl functional groups of pectin can act as a natural donor of electrons for free radicals quenching and exert pectin’s immunomodulatory and antioxidant potential [26].

Furthermore, it is possible that the high-viscosity pectin can form a thicker layer of mucous on the intestinal mucosa surface, thereby limiting the intestinal mucosa’s ability to absorb ingested carbohydrates and decreasing glucose absorption [29]. Pectin can slow down the contact time between ingested foods and enzymes in the intestine by holding food components in the intestine and by providing a thick layer coating on food fragments, which reduces the amount of food that is absorbed [30, 31]. Due to their higher water-binding capacity, pectin can provide a feeling of fullness and is useful in treating overeating disorders [32]. Furthermore, pectin’s capacity to extend stomach emptying and produce a longer-lasting sensation of “fuller” may significantly reduce the urge to eat [33, 34]. By slowing down the emptying of the stomach, reducing the diffusion of glucose, and reducing the absorption and storage of fat, pectin has been linked to weight loss [35, 36, 37]. Because pectin can form gels to swell in the aqueous surroundings of gastric fluids through self-association, this can stick to the stomach walls and bind to bile acids and the micelle components, such as cholesterol, free fatty acids, and monoglycerides, to decrease the absorption of fat in the stomach [38, 39, 40]. The high methoxy pectin can form a gel network with mucin, present in the intestinal epithelium via hydrogen bonds, and can give strength to the mucus layer and provide protection of intestinal epithelium against unwanted mucus penetrating materials. Meanwhile, low-methoxy pectin is capable of penetrating the mucus membrane to get into the intestinal epithelium and can excite intestinal mucosal epithelial cells to secrete the mucus. Thereby promote the protection of intestinal epithelium. Pectin can be degraded by pectinolytic enzymes produced by the gut microbiota in the colon. The decomposed pectin is used by intestinal microflora as prebiotics; through this, pectin can boost the growth and viability of probiotic strains from the gut and can contribute to the strengthening of the gastrointestinal immune system. Pectin can have an anti-adherence effect on pathogens and promote the adhesion of beneficial bacteria. This property can help to replace the pathogenic bacteria in the intestine [26]. In addition, pectin showed cholesterol-decreasing effects in humans [41, 42, 43, 44].

Pectin may aid in combating different types of cancer in several ways. Pectin has been shown to enhance immune function, control blood sugar, support the growth and viability of probiotics, regulate oncogenes, cause cancer cells to undergo apoptosis, inhibit the growth and development of tumors, and have effects that are anti-inflammatory, antioxidant, and wound healing [45, 46]. Pectin and its derivatives have been shown in several preclinical studies to effectively suppress cancer cells including the colon [47], liver [48], prostate cancer [49], bladder cancer [50], breast [51], and lung [52]. Pectin has intrinsic antitumor potential because it can identify and bind to the galectin-3 receptors that are found on different types of cancer cells. This has led to the evolution of many pectin-based nano-formulations for the delivery of chemotherapeutic medications [26]. Numerous systemic illnesses, including cancer, may be made worse by gut inflammation [53]. Pectin can modify symbiotic flora, inflammatory-associated cytokines, chemokines, intercellular adhesion molecules, and the gastrointestinal (GI) immune system [54, 55, 56]. Pectin is thought to have anti-inflammatory and immunomodulatory properties through a microflora-independent mechanism such as inhibiting the deterioration of the colonic mucosa barrier [57], influencing nonimmune and immune cells and attaching themselves to pathogens or toxins [58], and through a microflora-dependent pathway by associating with stomach bacteria, enhancing their metabolic processes, healing gut microorganism disorders, and delivering anti-inflammatory properties [56].

Moreover, atherosclerosis, metabolic problems (obesity and diabetes mellitus), diseases of the liver and pancreas, and hypoglycemia are all treated and prevented with pectin. It has been established that pectin act as protective agents against enzymatic proteolysis. Pectin-stabilized polypeptide medications, therefore, remain intact in the stomach and small intestine and subsequently release drug molecules once pectin is broken down by the colon’s microbiota [26]. One drawback of utilizing pectin by itself is that, due to its tendency to swell under physiological conditions, it releases drugs prematurely from the body [48]. Pectin mixtures with other polymers help to reduce this effect.

5. Microencapsulation

The technique known as “microencapsulation” involves the physicochemical or mechanical encapsulation of one material in another to create particles that are between nanometers and millimeters. The benefits of microencapsulation, including enhanced thermostability, protection of bioactive compounds, controlled release, preservation of volatiles, odor shelter, and improved texture/sense, have led to its strong recommendation in the food sector these days. A range of molecular interactions, such as van der Waals force of attraction, electrostatic force of attraction, and hydrogen bonding, are used to microencapsulate core materials in multilayers of wall materials. The wall materials are engineered to guide the core to its intended place while accommodating varying environmental conditions. Ultimately, as the microencapsulation system passes through the human digestive system, it should be able to dissolve in a gastric environment, and then the encapsulated core ingredients are delivered and absorbed in the intestine [1]. Pectin is a promising encapsulation material due to its many advantages, including its ability to stabilize emulsions, non-toxic nature, gelling, and binding properties [59].

5.1 Techniques used for the development of microencapsulation systems

The microencapsulation system using pectin can be created using different techniques. The major ones are discussed below.

5.1.1 Spray-drying technique

In the spray-drying method, the microencapsulation system is generated by atomizing the emulsion of the wall and core materials in a high-temperature environment. This process quickly hardens the droplet shell to encase the core material and evaporates moisture by heat transfer between the drying medium and droplets. This is the most popular embedding technology. This coating approach is cost-effective (30–50 times less expensive than freeze-drying), easy to use, capable of continuous production, and suitable for large-scale manufacturing. Better water solubility and low viscosity are necessary for wall materials to be suitable for the spray-drying process [1, 60].

5.1.2 Emulsification technique

Emulsification involves a chemical embedding process in which a mixture of dispersed phase, that is, core and wall materials, is combined with a significant amount of continuous phase, that is, vegetable oil containing the emulsifier. And form a stable emulsion, then microencapsulate with the help of a crosslinking agent. With the ease of use and excellent survival rate of encapsulated bioactive components, this technology allowed for a realistic preparation process; however, the enormous volume of vegetable oil required meant that manufacturing costs were typically very high [1].

5.1.3 Freeze-drying technique

The sublimation of ice into vapor using high vacuum conditions following a rapid freeze is known as freeze-drying. The process of ice sublimation eliminates heat and maintains a cool environment, hence maintaining the biological samples’ activity, including proteins. Nevertheless, the microbial cell membrane’s integrity may be compromised by the production of ice crystals and the higher osmotic pressure during the freeze-drying process. For this reason, hydrophilic material is typically added to the solution as a cryoprotectant. The freeze-drying technology is more often employed for high-value, heat-sensitive foods due to its high cost [1].

5.1.4 Coacervation technique

In the coacervation method, after suspending the core ingredient in the wall material solution, a different solvent or material is introduced to lessen the solvability of the wall material, which is then uniformly aggregated and occupied around the core substance to create microcapsules. Both the complicated condensation and the single condensation are part of the coacervation procedure. Two oppositely charged materials are employed as wall materials in the complicated coacervation, while the core ingredients are emulsified and distributed within the solution of wall materials. By interacting with the opposing charges, the two wall materials and the core substance combine to produce microcapsules by controlling the pH, concentration, and temperature of the system’s aqueous solution. Complex coacervation is a popular method for encasing fat-soluble food materials. It has the following benefits: less damage to the quality of the core material, mild process conditions, antioxidation efficiency, controlled core release properties, and higher product encapsulation efficiency [1, 60].

5.1.5 Layer-by-layer self-assembly technique

In LbL assembly techniques, the multilayers spontaneously adhere to one another to create stable supramolecular structures or molecular aggregates with particular performances or functions resulting from noncovalent interactions such as hydrogen bonds, coordination bonds, and electrostatic attraction. Accurate nanoscale control over the capsule’s shape, size, thickness, composition, and structure is achieved through the use of LbL assembly technology. As a result, LbL assembly technology presents itself as a viable technique for creating multilayer microcapsules that adapt to changing environmental conditions [1, 59].

5.1.6 Extrusion technique

Squeezing the colloid mixture and core material into the hardening bath as liquid droplets through using a needle-like tube under pressure is known as extrusion, and it is a physical embedding technique used to make microcapsules. The cost of this method is twice as high as that of the spray-drying method; however, the formed micropores have a small surface area, which allows them to successfully protect oil and oxygen from volatilization and improve product shelf-life. Pigment, vitamin, and volatile chemicals of all kinds, as well as other heat-sensitive components, are frequently embedded using the extrusion approach [5, 60].

5.1.7 Electrospray technique

Electrospray is a technique that breaks down the polymer fluid into small droplets using an electric field. This procedure involves a polymeric solution that is flowing out of a capillary nozzle, which is kept at high potential and subjected to an electric field. A jet forms when the electric field reaches a threshold value. The jet then deformed and dispersed due to the electric field, creating droplets. Once the solvent has evaporated, fine polymer particles are produced. Which is then collected using a metal collector to get the microcapsules. This eco-friendly method can be implemented without the need for extra reaction solvents. The uniform and nanoscale size of microcapsules created via electrostatic spraying has garnered increasing interest. The food and pharmaceutical industries are making significant use of the electrospray technique due to its immense potential for encapsulating volatile molecules, bioactive compounds, controlled-release additives, and functional foods [1, 59].

6. Pectin-based encapsulation systems and its applications in nutraceutical encapsulation

Nutraceuticals are dietary supplements that provide therapeutic or health benefits. These supplements contain bioactive nutrients in significant concentrations and dosages compared to the nutrients that our bodies ordinarily absorb from a regular diet. Dr. Stephen D. Feliz, who is regarded as the founder of nutraceuticals, first used the phrase “nutraceutical” in 1989. Thus, the term nutraceuticals came from nutrition and pharmaceuticals. In recent years, the nutritional value of several foods has been diminishing due to the use of hazardous chemicals, pesticides, and artificial fruit and vegetable ripening in agricultural practices. In the long term, a lack of vitamins, minerals, proteins, carbs, fats, and other nutrients will result in a variety of diseases due to insufficient daily intake. Nutraceuticals are a key component in closing the nutrition gap and achieving optimal nutrition [61]. Pectin is incredibly effective at increasing the stability and bioavailability of encapsulated nutraceuticals. The commonly utilized pectin-based encapsulation systems and their applications in nutraceutical encapsulation are covered in the section below.

6.1 Pectin-based hydrogels

Hydrogels are materials composed of crosslinked polymers in three dimensions that possess the capacity to absorb and hold vast amounts of water. According to studies [62, 63], hydrogels are used to enhance the water solubility and release characteristics as well as the stability of encapsulated compounds. They can be engineered to respond to stimuli by shrinking, swelling, as well as disintegrating in response to particular environmental factors including pH, enzyme activity, temperature, or ionic strength. The hydrogels’ pores can encapsulate bioactive materials [64, 65]. Hydrogel particles have the capacity to enclose bioactive substances that are both hydrophilic and lipophilic [66]. Proteins and polysaccharides, such as pectin, are the widely utilized polymers to make hydrogels [67]. The biocompatible and biodegradable nature of pectin is a clear advantage for encapsulating bioactive components. However, pectin formulations have less mechanical strength, which may make them susceptible to low drug loading efficiency and premature drug release. The drawbacks of pectin can be alleviated by developing pectin-based formulations using physical (polymer blending) and chemical (graft copolymerization and amidation) modifying techniques.

By using the graft copolymerization technique, scientists created a pH-sensitive polyacrylamide grafted pectin hydrogel that excelled at pectin in terms of gelling and film-forming ability. They discovered that the formed hydrogels were biocompatible and showed pH sensitivity and increased cell viability of B-16 melanoma cells [68]. In another study, they altered pectin using the amidation reaction, employing methanol as the solvent. The ethanolamine chemically modified pectin, and the resultant product, was used to create hydrogel that was crosslinked with glutaraldehyde. A substantial increase in gelling and film-forming capabilities was observed upon the addition of amide groups to pectin. They found that amidated pectin has a good swelling property. Which helps the effective release of salicylic acid at colon pH for an extended period. The hydrogel created in this study was found to have good cell viability with B-16 melanoma cells [69].

Peng et al. employed bovine serum albumin (BSA) and citrus peel pectin to make nanohydrogel by using a self-assembly approach to encapsulate vitamin C. After 10 days of storage, they discovered that the nanohydrogel system maintained its stability at about 73.95% and that the efficiency of vitamin C encapsulation was approximately 65.31%. They also concluded that this hydrogel that self-assembles could be used as a possible delivery method to increase the stability and bioavailability of functional chemicals [70]. In a different study, curcumin was delivered orally using nanogels made of low-density lipoprotein and pectin [71, 72]. Consequently, the generated nanogels facilitated the controlled release of curcumin and showed a fine surface with a homogeneous distribution in size.

Various researchers have also employed a modification of pectin to create drug-delivery devices. Commercial low-methoxy pectin and charge-modified high-methoxy pectin were utilized to develop hydrogel beads to encapsulate the drug, indomethacin [73]. The researchers discovered that the efficiency of the encapsulating system was improved with the use of modified pectin, which helped control the release of indomethacin at various pH levels. In another study, encapsulated doxorubicin (an anticancer medication) in a hydrogel that used oxidized pectin. According to their findings, doxorubicin-releasing oxidized pectin hydrogels can stop the development of metastatic cancer in addition to slowing the advancement of primary cancer [74].

6.2 Pectin-based micro/nanoparticles

Polysaccharide-based micro/nanoparticles are classified as colloidal particles since they primarily contain polysaccharide molecules inside of them instead of water. The physicochemical features and functional performance of this type of encapsulation system, including its stability, encapsulation effectiveness, loading capacity, and release profile, can be modified by adjusting its size, shape, composition, and charge [67]. Pectin-based micro/nanoparticles take on more importance, due to their biodegradable nature and ease of digestion by the intestinal microbiota.

Yu et al. created composite microparticles using pectin, alginate, and chitosan for oral delivery of proteins. Bovine serum albumin (BSA) was used as a model protein. In this study, the microparticles were created by using tripolyphosphate crosslinking, ionic gelation of calcium ions, and electrostatic complexation of alginate and pectin. They proposed that target-specific protein delivery through oral administration could be facilitated by the microparticles due to its better pH sensitivity [75].

Jones and team examined how the charge density of polysaccharides affects the generation and characteristics of nanoparticles made by thermal treatment of β-lactoglobulin-pectin complexes. They proposed that the type of pectin utilized affects the stability and size of the particles; that is, high, methoxy pectin produces smaller and more pH stable particles than low-methoxy pectin. Then, the biopolymer nanoparticles seem to be mostly composed of aggregated protein molecules; however, at pH values where there is sufficient electrostatic attraction between protein and polysaccharide, they are most likely complexed with pectin. They concluded that the developed protein–pectin nanoparticles may utilized as encapsulation systems in food industries [76].

Pectin was investigated for the suppression of agglomeration of human serum albumin (HSA) nanoparticles loaded with ciprofloxacin [77]. By using the pH-coacervation approach, HSA-pectin nanoparticles loaded with ciprofloxacin were created, and their various physicochemical properties were assessed. The scientists proposed using pectin as a pharmaceutical additive to decrease the particle agglomeration in HSA nanoparticles. Verma et al. created pectin nanoparticles and evaluated their effectiveness as a drug delivery system for paclitaxel, an anticancer drug. The authors proposed that the amide group of L-asparagine and the carboxylate and hydroxyl ions of pectin were actively involved in the process that formed the nanoparticles. Over the course of a month, the drug’s release pattern was biphasic, releasing 96% of the drug at pH 5.8 and 81% at pH 7.4 [78].

Resveratrol is a polyphenol derived from plants. It has garnered attention recently because of its potential health benefits, which include cardio and neuroprotection, hepatoprotection, anti-aging, antioxidant, anti-carcinogenic and anti-inflammatory properties [79]. Huang et al. encapsulated resveratrol using pectin–zein complex nanoparticles. This approach produced nanoparticles with a yield of 91.7% and a resveratrol content of about 10.2% (w/w). The nanoparticle loading efficiency of resveratrol was 77.9%. When compared to free resveratrol, the resulting encapsulated form of resveratrol exhibited increased antioxidant and anticancer effects. According to the study’s findings, resveratrol-loaded biopolymer nanoparticles may be useful in health supplements and food and beverage products [79]. In another study, the resveratrol was encapsulated in gellan gum/pectin blend nanoparticles using the ionotropic gelation process. The permeability of the nanoparticles and their sustained release pattern was evaluated in the Caco-2 cell model and the mucus-secreting tripe co-culture model [80]. They found that particles can load high concentration of drug (over 80%) in an acidic media with a low pH in 2 h and sustained resveratrol release of up to 85% in 30 hours in a pH 6.8 media.

In another investigation, pectin nanoparticles were created utilizing food-grade cassava root material to coat the nutritional supplement β-carotene, with the goal of increasing the bioavailability of these lipophilic dietary nutraceuticals during gastrointestinal (GI) delivery. The particles have a mean size of 21.3 nm, are mucoadhesive, and have enhanced antioxidant activity, bioavailability, and stability up to 90 days at 4°C [81]. Researchers developed caseinate/pectin-based phytosterol nanoparticles by combining emulsification, evaporation, and complex coacervation processes. These protein/polysaccharide composite nanoparticles demonstrated a significant phytosterol loading capacity (21%) and encapsulation efficiency (91%). The findings showed that the nanoparticles effectively encapsulated and protected the phytosterols while remaining stable throughout a 15-day storage period at 4°C and 25°C [82].

Curcumin-loaded nanoparticles with over 86% encapsulation effectiveness were created by a study [83] using zein-pectin complexation. According to their findings, the same method’s nanoparticles can be useful for incorporating curcumin as a pharmaceutical product. In another study, high methoxy pectin and sodium caseinate were employed to create nanoparticles, and it was discovered that the electrostatic interaction between the sodium caseinate and high methoxy pectin-based nanoparticles was stable across a range of pH values [84].

Eugenol essential oil is a natural phenolic compound derived from cloves and is valued for its potent antibacterial and antioxidant properties [85]. According to a study, zein-pectin-sodium caseinate complex nanoparticles can encapsulate eugenol. As an amphiphilic protein, sodium caseinate forms the intermediate layer between the hydrophilic pectin polymer and the hydrophobic zein polymer. The highly hydrophobic zein protein is positioned in the center of the complex structure of this nanoparticle, while pectin is in the outermost layer due to its higher affinity toward water [85].

6.3 Pectin-based nanofibers

Nanofibers-based encapsulation systems are composed of fibers that have sizes between one and one hundred nanometers [86]. These materials’ high surface area to volume ratio is beneficial for the sustained release of several active ingredients [87]. Electrospinning is one of the most utilized methods to make nanofibers due to its ease of use and efficiency [88]. Polysaccharide solution is pulled through a pump in the presence of a high electrical field during the electrospinning process. This creates a jet of fluid followed by solvent evaporation and solidification. Then, the resulting nanofibers deposit on the collector plate [89]. The crosslinking capacity of pectin-based formulations makes them suitable for the preparation of nanofibers. Additionally, due to their ability to mimic the structure of the natural extracellular matrix, electrospun pectin nanofibers offers unique advantages.

Tomasula et al. created ultrafine fibers using the electrospinning method. They used pullulan and pectin to create fibers. Lactobacillus rhamnosus GG, a probiotic, is used as a model bioactive component to demonstrate how the generated fibers may incorporate and preserve bioactive compounds. They showed that the generated fibrous mats have a potential for the food industry [90]. In another investigation, water-resistant pectin nanofibers were effectively produced using electrospun synthesis with different types of pectin (HMP and LMP). This study concluded that drug delivery could be facilitated by the use of manufactured nanofibers [91]. Folic acid was encapsulated in pectin-poly (ethylene oxide)-alginate electrospun nanofibers [92]. The study revealed that folic acid encapsulated in the pectin-alginate system shows high folic acid retention when compared to alginate alone encapsulation system. The recovery of folic acid encapsulated with nanofibers was about 100% when it was stored in the dark at pH 3 for nearly 41 days. On the other hand, the retention of unencapsulated folic acid was found to be insignificant. Furthermore, other studies also successfully created electrospun-coated nanofibers utilizing polyethylene oxide and pectin, with the conclusion that these pectin-based nanofibers have prospective uses in biomedicine [93, 94].

6.4 Pectin-based micro/nanocapsules

Nanocapsules are small particles with a core and shell structure. The protection and distribution of bioactive substances have been extensively employed with nano- capsules [95]. A polymer shell encircling a fluid center is their typical structure. Since less polymer is needed to generate the delivery systems with nanocapsules than with nanoparticles, this is an advantage [96]. The utilization of polysaccharide-shelled nanocapsules has been observed to mitigate immunological elimination and extend their circulation in the body [97].

A study investigated the encapsulation of Bifidobacterium probiotics in pectin-and alginate-based microcapsules using the emulsification/internal gelation process. When compared to its alginate counterpart, pectin, as the wall material used in microencapsulation, had a better encapsulation yield (89.5–96.9%). It also retained a higher probiotic viability after freeze-drying and in the simulated infant gastrointestinal digestion [98]. Osteopontin (OPN), an acidic glycoprotein, usually found in human and domestic animal milk. It has been related to early life developments, including immunological modulation, intestinal development, and nervous system development [99]. They found that, using OPN as the excipient for pectin-based microencapsulation systems further enhanced the probiotic viability even more in challenging circumstances. After intestinal digestion, non-microencapsulated Bifidobacterium bifidum R0071 and Bifidobacterium breve M-16 V showed markedly decreased viability. While all strains of Bifidobacterium in pectin and alginate-based microcapsules retained much higher viability (8–9 log CFU.mL⁻¹). Even though the intestinal phase of the microencapsulation showed a decline in probiotic viability compared to the stomach phase, encapsulation was still able to effectively shield Bifidobacterium strains throughout intestinal digestion [98]. In a different investigation, the Lactobacillus acidophilus LMG9433 encapsulated microcapsule using low-methoxy pectin developed and found that probiotics were significantly protected during intestinal digestion. They discovered that the microcapsule had higher probiotic viability (8 log CFU.mL⁻¹) in comparison to the free bacterial cell sample (5 log CFU.mL⁻¹) [100].

Whey protein–pectin nano spray-dried microcapsules were created by a study to encapsulate grape marc phenolics and investigate the impact on the stability and bioaccessibility of the polyphenols. Enhancing bioaccessibility, the new encapsulating technique preserved the antioxidant activity of grape marc phenolics during simulated gastrointestinal digestion (GID). Results suggest that this encapsulation method could be an effective strategy for maintaining the phenolic’s antioxidant properties [101].

Curcumin is the major component of turmeric, it gives its medicinal qualities such as antioxidant abilities, anticancer, and anti-inflammatory activity [102]. It is a biologically active molecule that is typically utilized as a model for nutrition and medicine [103]. Yan et al. created nanocapsules and encapsulated curcumin using the electrostatic interaction between pectin and heat-denatured lactoferrin. With a loading capacity of 13.4%, the simulated complex demonstrated an encapsulation efficiency of almost 85.3%. The authors also concluded that the generated nanocapsules, enhanced curcumin solubility and antioxidant capacity, can be used as an appropriate delivery mechanism for sustained release [104].

To deliver the anticancer medication doxorubicin hydrochloride, researchers created a hollow nanocapsule with pectin and chitosan using a layer-by-layer technique. They reported that the nanocapsules exhibited a high loading capacity, good biocompatibility, and pH sensitivity [105].

6.5 Pectin-based nanoemulsions

Emulsions are combinations of two or more liquids that are usually immiscible in nature. The two immiscible liquids found in food are usually an oil phase and a water phase. Nanoemulsions are encapsulation systems that normally have an average diameter of between 50 and 200 nm [106]. Because of their excellent physical stability, great optical transparency, and capacity to increase the bioavailability of encapsulated drugs, nanoemulsions are frequently utilized as delivery vehicles for bioactive components [107]. Based on the relative spatial arrangement of the water and oil phases, nanoemulsions can be categorized as oil-in-water (O/W), water-in-oil (W/O), oil-in-water-in-oil (O/W/O), or water-in-oil-in-water (W/O/W) forms [108]. W/O nanoemulsions are utilized to encapsulate hydrophilic components like vitamin C, polyphenols, whereas O/W nanoemulsions are typically used to deliver hydrophobic bioactive components like carotenoids, vitamins, omega-3 fatty acids, essential oils, and curcuminoids. O/W nanoemulsions can be stabilized by polysaccharides. The polysaccharides attach themselves to the surfaces of the oil droplets and create a barrier that keeps the droplets from aggregating together. Moreover, polysaccharides can be combined with other molecules to generate conjugates that are surface-active and useful for stabilizing O/W nanoemulsions [109, 110].

Due to properties such as natural colorants and antioxidants, saffron is a chemical that is frequently employed in the food and pharmaceutical industries. It comprises bioactive constituents such as safranal, picrocrocin, and crocin. In a study, researchers created a nanoencapsulation system for saffron extract using spray-drying and double-layered emulsion utilizing whey protein concentrate and pectin, respectively. With excellent encapsulation effectiveness, these scientists were able to generate particles with a size of less than 100 nm that were devoid of pores and cracks [111].

The efficiency of low-methoxy pectin (LMP) and whey protein isolate (WPI) based complexes on the regulated release of vitamin E and vitamin B12 was investigated in a study using the double emulsion (W/O/W) method [112]. They found that the WPI–LMP complex system exhibit a 1.4-fold increase in the encapsulation efficiency of vitamin E and vitamin B12, when compared to the encapsulation efficiency of the WPI-only system. The rate of controlled release of these vitamins is also significantly improved by these complexes. The LMP shows more synergistic effects due to its diverse protein- and oil-binding capabilities. They concluded that pectin could therefore be used for nanoencapsulation, which can improve the bioaccessibility and allow for the regulated, targeted release of bioactive compounds under simulated gastric environments.

In another study, pectin-based nanoemulsions encapsulating the poorly water-soluble antifungal medication itraconazole (ITZ) were developed for use in pharmaceutical applications. They discovered that high methoxy pectin can act as a good emulsifier during the emulsion process due to its higher degree of esterification, which has a quantity of hydrophobic molecules. The discovery revealed that the molecular interaction between ITZ and pectin plays a key role in obtaining nanosized emulsion. They further suggested the possibility of using the produced nanoemulsions to develop self-emulsifying drug delivery systems [113].

6.6 Pectin-based nanoliposomes

The interactions that take place between hydrophobic polar lipid molecules, like phospholipids and hydrophilic water molecules, are typically used to generate liposomes. However, the instability of liposomes might cause changes in the distribution of particle sizes, leakage of encapsulated substances, and rapid oxidation, which limits their practical use. The generation of polymeric bio-adhesive membranes around the liposomes may help to improve this limitation [114]. Coating liposomes with a pectin biopolymer layer can improve their stability [115]. The non-toxic, biocompatible, and biodegradable nature of pectin makes it an effective choice as a coating layer for a liposome-based delivery method. Furthermore, because of its high mucoadhesive qualities and charge density, pectin can help enhance the targetability and stability of delivery systems like liposomes [116]. Zhou et al. reported that pectin-coated liposomes demonstrated the capacity to stabilize liposome-based drug delivery systems [114]. Another research has shown that pectin at a suitable concentration but with a lower degree of methylation (DM) can result in pectin-coated liposomes that are more stable and smaller in size [116].

Zhou et al. effectively created pectin-coated vitamin C encapsulated nanoliposomes in an effort to improve its stability and epidermal penetration. They discovered that low-methoxy pectin (LMP), might function as an efficient transdermal drug delivery system [114]. Pectin-based nanoliposomes were successfully generated by Haghighi et al. to encapsulate the biologically active polyphenol Phloridzin. They also observed that the pectin-coated nanoliposomes exhibit greater encapsulation effectiveness and stability when compared to non-coated nanoliposomes. Additionally, they concluded that the created pectin nanoliposomes loaded with Phloridzin could be a potential ingredient for use in both food and pharmaceutical goods [116].

Citrus fruits are a common source of Neohesperidin, a flavanone glycoside with a variety of biological actions, including anti-diabetic, anticancer, anti-inflammatory, anti-allergic, gastric protection, and neuroprotection. In order to enable sustained delivery of Neohesperidin in a simulated gastrointestinal environment, scientists created nanoliposomes by using chitosan and pectin molecules. The generated nanocarrier had a diameter of 87–225 nm. The researchers discovered that these nanoliposomes were allowed to retain 72.78% of the encapsulated substance in gastrointestinal settings and that they significantly controlled the release of Neohesperidin. They also concluded that these nanoliposomes could improve the cellular absorption of the colonic epithelial cells [117].

7. Conclusions

A new and promising avenue for the development of effective and practically useful encapsulating systems is the introduction of non-toxic, inexpensive, ecologically benign, and biocompatible biopolymers like pectin. Pectin, a ubiquitous natural biomaterial, is now an incredible matrix polymer for encapsulation. Pectin is very efficient in enhancing the bioavailability and stability of encapsulated bioactive substances. Additionally, as a molecule, it can be modified to meet certain objectives, such as controlled and targeted release of cargo and offer health advantages. Because of its potential for enhancing food quality and creating novel nutritional supplements, the technological application of these bioactive food ingredients impacts industrial development and inspires future multidisciplinary studies. To facilitate oral ingestion and more improved applications in food and pharmaceuticals, they must be used with safety requirements. Although pectin has been employed in food applications for ages, its usage in micro and nanoencapsulation is still relatively new. Future studies are expected to lead us to an advantageous situation where we can fully utilize the encapsulating potential of pectin by customizing its structures in a more evolved way on an industrial context.

Acknowledgments

We acknowledge the KSCSTE Research Fellowship, Kerala State Council for Science, Technology and Environment, Kerala, India.