4.2.3. Controlled Release of Ascorbic Acid

The challenge of ascorbic acid in food applications is not only to maintain its stability, but also to improve the effectiveness of delivery it to the active site. The release of bioactive compounds in the body is expected to occur in the intestine rather than the stomach, because the absorption mainly occurs in the small intestine. It was found that ascorbic

acid in pomegranate juice was approximately 29% degraded during gastric digestion, which severely reduced the bioavailability of ascorbic acid. Additionally, the compounds that are transported by specialized processes are usually only absorbed in certain parts of the gastrointestinal tract. The absorption of riboflavin begins in the upper region of the small intestine, as does ascorbic acid [101]. Therefore, the changes in gastric and intestinal transit rates may affect the absorption efficiency of orally administered bioactive compounds. Additionally, the bioavailability of oral ascorbic acid is related to the following key steps: (1) Release of ascorbic acid in the gastrointestinal tract, and its solubility in gastrointestinal fluids. (2) Intestinal epithelial cells absorb ascorbic acid and undergo biochemical transformation. Studies have shown that a single high dose of ascorbic acid causes a temporary increase in plasma that is rapidly absorbed by the gastrointestinal tract and then quickly excreted in the urine [102]. A form of ascorbic acid that can be slowly released in the intestine is desired to maintain a constant level of ascorbic acid in plasma.

The release process of encapsulated ascorbic acid is as follows: absorption of solvent by the carrier, dissolution of the wall-coating, and the diffusion of inner core. The release of bioactive compounds in carriers depends on many factors, such as the selection of the wall material, the ratio of wall/core, the size of the carrier, the solubility of the bioactive compound, and the release conditions [15,97]. Ascorbic acid releases kinetics from ascorbate gummies, which were investigated using an in vitro simulated digestion model. The results show that the disintegration time of ascorbic acid candy was about 22 min, after which the functional ingredient ascorbic acid was gradually released, reaching 93.6% within 2 h. Notably, the components in gastric juice may have an effect on the release of ascorbic acid, with gastric juice containing 5% starch slowing the release of bioactive ascorbic acid in the gummies, but other dietary components had no significant effect on its release [103]. This may be related to the encapsulation of ascorbic acid in starch in the stomach. Compared with the afore-mentioned delivery vehicles based on polysaccharide and lipid, the protein carrier has poor stability in the stomach. The low pH of the gastric environment and the presence of pepsin cause the denaturation and degradation of the protein carrier, leading to the leakage of loaded bioactive compounds in the stomach before reaching the small intestine [104]. Gelatin/pectin microcapsules show a high loading capacity of ascorbic acid. However, due to the dissolution of gelatin coating in the gastric environment, the release of ascorbic acid in the gastric environment is faster than in the intestine [15]. Therefore, it is necessary to design a carrier that is relatively stable in the stomach and which can provide a sustained release of ascorbic acid in the intestine.

The small size and positive charge of the particles contribute to the high uptake rate by intestinal cells. The loading in chitosan nanoparticles effectively prolong the residence time of ascorbic acid in the intestine of rainbow trout [16]. Nanoparticles based on chitosan with low molecular weight have a higher delivery rate of ascorbic acid. The mechanism of ascorbic acid released from nanoparticles in the gastric environment and the intestinal environment are diffusion and erosion, respectively. Under the neutral conditions of the intestine, the ion exchange between chitosan and the release medium leads to the erosion of nanoparticles. The release rate of ascorbic acid increased from 30% in the stomach to more than 75% in the intestine [16]. As reported, the water-soluble derivative N,N,Ntrimethylchitosan (TMC) as a carrier can efficiently transport hydrophilic molecules through mucosal epithelial tissues such as the oral cavity, nasal cavity, lungs and intestines [88]. Thus, the carriers based on chitosan coatings may be an effective strategy to achieve intestinal release of ascorbic acid. Based on the continuous deposition of positively charged chitosan and negatively charged sodium alginate on the surface of anionic nano-liposomes, a liposomal polyelectrolyte delivery system of ascorbic acid was prepared. The clinical results showed that the bioavailability of orally administered liposomal ascorbic acid was 1.77 times higher than that of non-liposomal ascorbic acid, with higher bioavailability [105]. The ability of the outer layer of chitosan to withstand the gastric environment is beneficial for maintaining the stability of the carrier structure. The excellent sealing properties of

liposomes and better penetration with enterocyte phospholipid bilayers also contributed to the improved bioavailability of released ascorbic acid.

#### **5. Commercial Application of Ascorbic Acid**

Based on the afore-mentioned biological activity of ascorbic acid, ascorbic acid is mainly used as an antioxidant to inhibit food browning and as a dietary supplement for humans. Ascorbic acid is mainly used as an antioxidant to protect the senses of foods. As is well known, polyphenol oxidase catalyzes the enzymatic browning of phenol substrates to yield dark-colored melanin. Browning affects product sensory qualities and reduces consumer acceptance. Adding xyloglucan microcapsules containing ascorbic acid to baked foods such as tilapia fish burgers can significantly inhibit the browning that occurs during the preparation process and maintain the sensory qualities of the product [93]. The chitosan/tripolyphosphate nano-aggregates containing ascorbic acid enhanced the inhibition of mushroom slices browning induced by tyrosinase [106]. Acute heat stress during transport is known to predispose rainbow trout quality to deterioration, with negative effects on the histological, physicochemical and microbiological quality of fillets. Treatment with added ascorbic acid partially mitigated damage caused by acute heat stress. It can maintain tissue structure, delay protein oxidation and then prolong the shelf life of fish fillets to about 2 days [107]. In addition, as a nutritional supplement, ascorbic acid plays an important role as a co-factor in many biological processes. Unfortunately, fishes lack L-gluconolactone oxidase and cannot biosynthesize ascorbic acid by themselves, which is not conducive to the growth of their bone matrix and connective tissue. Lack of ascorbic acid can cause reduced wound-healing capacity and bone deformities in fish [108]. At present, in the aquaculture area, ascorbic acid is widely added to fish diets. Based on the healthcare function of ascorbic acid, it is also vital in nutrition fortification products. As an important source of protein supplementation, dairy products are popular beverages all over the world. At present, milk and soymilk have been fortified with ascorbic acid, including ascorbate and ascorbic acid isomers, to improve the iron absorption in the small intestine [109,110].

Food fortification can improve micronutrient malnutrition. It is worth noting that a category of foods tailored according to the necessary nutrients for a healthy life and their specific concentrations and ratios are called designer foods, also known as health foods, and are sought after and recognized by consumers. Such products often contain a variety of bioactive compounds. By adding calcium and antioxidants such as vitamins E and C to low-fat chicken patties, a high-quality product with high-quality animal protein, fat, multivitamins and minerals can be prepared. Ascorbic acid not only acted as a nutritional additive, but also maintained better color and flavor of chicken patties, and inhibited the formation of nitrosamines in the meat [111]. The addition of sodium ascorbate and vitamin A to pig feed can significantly improve the growth performance, antioxidant capacity and immune function of weaned piglets. Meanwhile, as an antioxidant, sodium ascorbate can delay the degradation of vitamin A [112]. A cornstarch-based baking premix was developed by addition of vitamin B, vitamin C and digestible iron, zinc, selenium and iodine. Although the added ascorbic acid in the baked bread degraded due to high temperature, it strengthened the structure of the bread and was benefit to product quality [113]. Meanwhile, it was found that the combination of butylated hydroxytoluene and ascorbic acid significantly inhibited the oxidation and isomerization of vitamin A in skim milk powder during thermally accelerated storage [104].

There are two major aspects in the current development of ascorbic acid-fortified products. On the one hand, the natural ascorbic acid is directly added, in order to use its antioxidant activity to maintain the sensory appearance of the product during the shelf life. The cost is low, but the retention activity of the final product is low. Another aspect is the addition of ascorbic acid derivatives, which is to ensure that sufficient physiological activity can be expressed after ingestion of the product. However, the cost of ascorbic acid derivatives is high, and they need to be converted before they can exert their functional properties. The related products of ascorbic acid and its main derivatives in the food fields in recent years are summarized in Table 2. Although various delivery technologies are available, they are still in the developmental stage of industrial transformation and have not been widely used. Combined with the above analysis of delivery strategies, these may be limited by the cost of wall materials, and the complexity of the process, which is not suitable for large-scale industrial production. Therefore, researchers still need to explore low-cost, simple, and high-yield encapsulation techniques of ascorbic acid for industrial application.


**Table 2.** Commercial products fortified with ascorbic acid and its derivatives.
