**2.1 Molecular weight**

Alginates obtained from different locations in a sea bed have different molecular weights ranges between 50,000 to 5lakhs [16]. The viscosity of the alginate solution

*Alginates - A Seaweed Product: Its Properties and Applications DOI: http://dx.doi.org/10.5772/intechopen.98831*

**Figure 2.**

*Structure of Alginic acids with 1, 4 linkages between L-Guluronic acid (G) and D-Mannuronic acid (M) [11].*

is pH-responsive and increase viscosity is reported with the decrease in pH and reaches a pH ~ 3.5 because carboxylate groups in Guluronic acid present in the alginate structure protonated and form hydrogen bonds [17]. Alginates may have different molecular weights depending on whether they need to monitor pre-gel solution viscosity or post-gelling strength distribution separately. To adjust the viscosity of the solution, a mixture of high and low molecular weight alginate polymers is used [18].

## **2.2 Biocompatibility**

The biocompatibility of alginate has been extensively evaluated *in-vitro* as well as *in-vivo* at varying levels of purity. It has been reported that alginate containing high M monomers are more immunogenic and 10 times more effective in promoting cytokine synthesis compared to G monomer in alginates [19], but others reported very little response or no immune response across alginate implants [20]. Impurities in the alginates, such as heavy metals, endotoxins, proteins, and polyphenolic compounds, may be causing the variable reaction at the injection or implantation sites. However, not many serious inflammatory results were reported in commercially available or certified or alginates obtained from branded companies [21].

#### **2.3 Alginate derivatives**

Alginates are exploited or synthesized for various biomedical applications by introducing different hydrophilic moieties such as alkyl groups or hydrophilic polymers in the alginate matrix. Long-chain alkyl groups such as dodecyl or octadecyl are bonded with alginates matrix *via* esterification. The various properties such as rheology, gelling and crosslinking characteristics are very useful in bone regeneration and cartilage repair [22]. Sustained or controlled drug delivery vehicles are achieved from alginate derived from Poly (butyl methacrylate) [23].

Alginates are also investigated for their derivatives with cell-adhesive peptides are prepared by adding peptides as side chains and coupled through the carboxylic groups of the sugar residues [24, 25].

#### **2.4 Gelling properties**

The ability of aqueous alginate solutions to form gels when treated with divalent ions (Ca2+, Sr2+, and Ba2+) or trivalent ions (Fe3+ and Al3+) ions has been extensively explored for the fabrication of carriers for sustained or controlled delivery of therapeutic agents. This is due to intramolecular bonding and ionic interactions that exist within the carboxylic acid groups on the polymer matrix and the cations present as shown in **Figure 2** [26, 27].

The calcium or any other divalent or trivalent ions will interact with the G monomer present in the alginate structure to crosslink with another molecule, and the structure is identical to the egg box model (**Figure 3**) [28].

The complexing forming agents such as EDTA-sodium citrate [29] or monovalent cations, complex anions (phosphate, and citrate) which have a high affinity for Ca2+ions, which can disrupt calcium alginate gels easily. The presence of high concentrations of non-gelling ions (Na<sup>+</sup> and Mg2+) also contributes to the instability. It was reported that the strength and uniformity of gelling largely depend on the type of crosslinking and temperature [30].

It is also reported that the strength of alginate film with Al3+ ion is very low compared to other divalent ions (Ca2+ and Ba2+) crosslinking because in the case of Al3+ ions the crosslinking occurs in two different planes of the alginate structure and at the same time it makes the alginate framework more compact [31]. The small size of the Al3+ ion (0.58 A) facilitates its diffusion into the matrix of the film without crosslinking on the surface and thus results in poor crosslinking [32].

For a variety of uses, including tissue engineering, alginates are being investigated for covalent bonding to enhance the physical properties of gels. In the case of alginates with covalent bonding degradation of chain occurs even with a slight increase in temperature due to breaking of crosslinks ultimately leading to stress relaxation due to water migration. It was reported that covalently bonded alginates are found to be toxic [33]. Furthermore, the Ca2+ ions released out of the gel can boost hemostasis, while the gel acts as a matrix for platelet and erythrocyte aggregation [34].

To prepare gels with a wide spectrum of mechanical properties, covalent crosslinking of alginate with Poly (ethylene glycol)-diamines of different molecular weights was first investigated. The elastic modulus showed improvement in gel with crosslinking density or weight fraction of Polyethylene glycol (PEG), but then decreased as the molecular weight between cross-links increased became less compared to the original PEG [35]. Using various types of cross-linking molecules and regulating cross-linking densities, it was later investigated that the mechanical properties, as well as swelling of alginate strength, are tightly regulated. As most would imagine, the chemistry of the cross-linking molecules has a major impact on hydrogel swelling. While shaping hydrogels, multi-functional

*Alginates - A Seaweed Product: Its Properties and Applications DOI: http://dx.doi.org/10.5772/intechopen.98831*

cross-linking entities have a greater scope of degradation efficiency and mechanical strength performance than bi-functional cross-linking molecules. Physical properties and degradation behavior of Poly-aldehyde guluronate (PAG) gels are prepared with either Poly-acrylamide-co-hydrazide (PAH) or Adipic acid dihydrazide (AAD) as a cross-linking agent were investigated *in-vitro*. PAG/PAH gels had higher mechanical stiffness and very low degradation is observed compared to PAG/AAD gels [36].

Photo crosslinking is used for crosslinking in alginates structures under mild conditions either direct or indirect sunlight or in the presence of suitable initiators. For example, the mechanical properties of Polyallylamine and alginate were significantly improved from this technique [37].

### **2.5 Solubility**

The alginates with divalent or trivalent cations are not soluble in water because the alginates contain a terminal carboxylic ion (–COO-), so these cations bond to this and yield an insoluble product. As a consequence, the alternative is the absorption of as much as 200–300 times their weight in water, thus swelling to a hydrogel of paste-like consistency. However, alginates with monovalent cations (Na+ , K+ , and NH4+ ) are soluble in hot and cold water. Alginates have a wide range of solubilities due to their different molecular weights.

Alginates derived from Ascophyllum, for example, have aqueous solubility in the range of 22–30% weight percent, whereas those of two Laminaria groups are 17–33% weight percent and 25–44% weight percent, respectively [38, 39].

#### **2.6 Effect of pH on alginates**

The solubility of alginates was influenced by parameters such as pH and ionic strength. Alginates have very low solubility in lower pH values due to the deprotonation of carboxylic groups (–COO-). The viscosity of alginates is unaffected above pH > 5, whereas solution having pH < 5, the COO- group present in alginates gets protonated to –COOH, and the electrostatic repulsion between chains decreases, they can move closer together to form hydrogen bonds, whereby the viscosity decreases [40]. It has been reported pH > 11 alginates viscosity is reduced due to de-polymerization [41].

The concentration of ionic solution influences the crosslinking, which increases the viscosity and molecular weight of alginates [39, 42]. Furthermore, the crosslinking depends on the confirmation of monomers G and M groups present in the alginate matrix.

#### **2.7 Sterilization**

It is reported that the viscosity of alginates decreases with autoclave sterilization because the heating randomly breaks alginate chains. The degree to which this loss occurs is determined by the presence of other kinds of stuff in the solution. Alginate solutions have also been sterilized using ɤ-radiation and ethylene oxide [43].

#### **2.8 Immunogenicity**

Control drug delivery is the latest trend in the presence of pharmaceutical dosage requirements for successful application in drug carriers; alginates play an important role because of their biocompatibility and immunogenicity [44].

#### *Properties and Applications of Alginates*

The two key factors responsible for alginate immunogenicity are its chemical composition and the mitogenic pollutants present in alginates [45]. When alginate comes into contact with blood, it is believed to have mild cytotoxic effects and decreased hemolysis.

#### **2.9 Biocompatibility**

The biocompatibility and strength of alginic acid are determined by the quantity and quality of the acid. Furthermore, the impacts of the quantity of G monomer on alginate biocompatibility are still under investigation. Experts find different opinions on the G content of extremely purified alginate rich in G monomer residues, while others have emphasized the importance of high purity while ignoring the effects of chemical composition [46]. Animals such as rats are injected in their kidney parts with calcium alginate for biocompatibility studies and the results obtained are very promising [45].

Alginates are also experimented on in mammals and observed that they could not digest because they lack the enzyme '*Alginase*' that can break the polymer chains. Whereas ionically cross-linked alginate gels undergo dissolution by replacing the divalent crosslinked gel with monovalent cations into the surrounding media. Even alginates dissolve in the body they cannot be expelled from the body because of its high molecular weight are higher than renal clearance [47]. It is reported, alginates were obtained from *Undaria pinnatifida*, a brown seaweed invasive in the Argentinian coast are found to be toxic, but its purification using commercial techniques improves its biocompatibility and eliminates cytotoxicity in an alginate matrix for bone tissue engineering [48].

#### **2.10 Bioadhesion**

The binding or contact between two surfaces, one among being a biological substrate, is known as bioadhesion [49]. Mucoadhesion is an example in which the mucosal layer used. The carboxyl group in alginates represents a mucoadhesive anionic polymeric layer. It was reported polyanion polymers are more efficient bioadhesives compared to polycation or non-ionic polymers [50]. Alginate has better mucoadhesive strength as compared to polymers like Polystyrene, Chitosan, Carboxymethyl cellulose, and Poly (lactic acid). The bioadhesive properties of alginate would be advantageous as a mucosal drug delivery vehicle to the GI tract and nasopharynx by extending drug residence time at the site of action making them more effective [44, 51, 52].

#### **2.11 Toxicity**

Plenty of studies are reported that alginates especially crosslinked sodium/calcium alginates are non-toxic to cells, even not shown any irritation to eyes and skin [53]. Because of the nontoxicity, they found various applications in drug delivery, cosmetics, and food industries.

## **3. Applications of Alginates**

Alginates are available in plenty in oceans and because of their diverse properties such as biodegradation, biodegradable, non-toxic, etc., as mentioned above; they have plenty of applications in the food industry, pharmaceuticals, cosmetics, textile industry, welding, and animal feeds, etc.
