**3. Molecular structure of alginate**

Alginates are natural anionic polysaccharides belonging to the family of linear copolymers (without branches) found in the cell wall matrix of brown seaweed [25].

Alginate is a general name that refers to a group of natural and non-branched polysaccharide polymers consisting of repeating units of α-L-Gluronic acid and β-D-Mannuronic acid linked by 4 → α1 bonds and having monochain sequences MMMMM and GGGGG together. It is formed by alternating sequences of MGMGMG (**Figure 2**).

The molecular weight of alginate varies in the range of 92–177 kg/mol along with different G/M ratios. Chain arrays based on the source of extraction and the age of algae have led to the commercialization of more than 277 types of alginate. In addition, the efficiency of drug delivery by alginate depends on the conditions of G/M ratio, molecular weight, concentration, and pH of the environment. One of the most

#### **Figure 2.**

*Structural characteristics of alginate: (A) alginate monomers, (B) chain structure, and (C) distribution of G and M blocks in alginate.*

#### *Alginate, Polymer Purified from Seaweed DOI: http://dx.doi.org/10.5772/intechopen.112666*

useful features of alginate is its ability to cross-link in aqueous solutions by a mechanism through the carboxylic acid part of the hanging G units with calcium ions and other divalent cations (such as Ba2+, Sr2+, Zn2+) to form a three-dimensional network. This gelation mechanism is explained by the "egg-box" model, in which a divalent cation reacts with 4 COOH- groups (**Figure 3**), which has been used for more than 3 decades to encapsulate a wide range of drugs, proteins, genes, and cells have been used. Another cation that has been used for cross-linking with alginate is Fe(III).

The mechanical and physical stability of alginate gels depends on its G content, the higher the G content, the greater the inflexibility and fragility of the matrix. Also, the process can be reversed in the presence of ion separators such as ethylenediaminetetraacetic acid (EDTA) and sodium citrate. In addition, alginate gels tend to degrade more in neutral and alkaline pH than in acidic conditions. These features encourage its use in chemical stabilization of drugs and oral administration of biological substances that are not stable in digestive tract fluids. From a legal point of view, the US Food and Drug Administration (FDA) has accepted alginate as a GRAS (Generally Referred as Safe) substance, a designation that is used for substances that are accepted for food use by certified professionals is located. In addition, alginate is bioadhesive, mucoadhesive, biocompatible, and hypoallergenic. Therefore, it is used in the production of adhesive molds for the oral delivery of medicine and wound covering with various characteristics, including absorption of secretions, moisture retention, and wound healing, and the production of three-dimensional scaffolds.

Due to its gelling properties, alginate is used in drug encapsulation as a drug delivery tank. In general, there have been many studies that confirm the use of alginate through different prescription ways. On the other hand, the production of alginates with high purity can pave the way for application programs aiming to be more compatible with living systems. Also, in order to improve the properties of alginate, its surface can be modified with other materials.

Due to the hydrophilic nature of alginate, the release of encapsulated drug cargo can follow different mechanisms. In relation to drugs enclosed in alginate polymer, water-soluble drugs are mostly released through diffusion, while drugs with low solubility in water are released through erosion of the alginate matrix. Also, the release of small molecules is faster due to the fact that a cavity with a diameter of about 5 nm is created in the swollen matrix of alginate. However, in order to prolong the release

#### **Figure 3.**

*A schematic representation of the surrounding of calcium ion in the "egg-box" model for the coupling of gluronate chains in the connection of calcium alginate. The black circles represent the oxygen atoms that are involved in surrounding the calcium ion.*

time of the drugs, various changes can be made in the physical and chemical connections of the encapsulated drugs in the polymer network. Also, the interesting feature of alginate is that in dry environments, they are mucus adhesive, which makes the retention and release time longer in various mucous tissues, such as intestines, lungs, nose, and eyes [19, 20].

Alginates are polysaccharides that are the most abundant among marine biopolymers, and after cellulose, they are the most abundant among biopolymers in the world. The process of extracting alginate from brown seaweed is a simple method and it is possible to extract this substance from dried brown algae by using diluted mineral acid and sodium carbonate. The usual use of alginate as an additive in pharmaceutical products generally depends on its gel formation and stability properties. During the gelation process, alginate gel can be prepared with three methods: syringe or dropper, extrusion method, and liquid method. The process of extracting alginate from seaweed is a simple but multi-step method that usually starts with the effect of diluted mineral acid on dried algae. In the next steps, the alginic acid obtained from the previous step is converted into water-soluble sodium salt in the presence of sodium carbonate, and the expected acid or salt can be obtained in the next step. Finally, the obtained sample is purified to be used in different applications (**Figure 4**).

The extraction of alginate can be summarized in five steps (**Figure 5**). First, the dried and crushed brown seaweeds were extracted with a mineral acid (e.g., HCl,

**Figure 4.** *Production of sodium alginate isolated from brown algae.*

#### **Figure 5.**

*Production process and applications of alginates.*

*Alginate, Polymer Purified from Seaweed DOI: http://dx.doi.org/10.5772/intechopen.112666*

0.1 M), leading to insoluble alginic acids which are easily separated from other contaminating glycans such as sulfated fucoidans and laminarans by filtration or centrifugation. The insoluble residue is then treated by alkaline solution (using sodium carbonate, sodium hydroxide, or aluminum hydroxide, above pH = 6.0) to convert insoluble alginic acid into sodium alginate. After another separation step, the soluble sodium alginate is precipitated using calcium chloride or cold alcohol. Alginates are then purified using techniques such as acidification, the addition of Ca +2 ions (calcium alginate formation), or the addition of ethanol (dielectric stabilizer) [26].
