**Abstract**

Alginate is a natural polymer that can form complexes in the presence of multivalent metal. In this chapter, we summarized the newest alginate metal complexes application in many fields; organic synthesis, environmental and medical application. The main idea was about alginate complexes' role in the drug delivery system as a chiral excipient to reach the enantioselective release in the case of chiral drugs. We also present a case study about the ketoprofen enantioselective release investigation from alginate mixed beads with two ion metal types.

**Keywords:** Alginate-metal complex, ionotropic method, chiral excipient, enantioselective release, enantiomers, chiral HPLC

## **1. Introduction**

Many publications in the last decade dealt with different applications of alginate in several fields. Alginates application is depending on its source, extraction methods, it's physiological characteristics, functions, and properties [1]. Developing alginate and its derivatives were designed in various formulations for biomedical applications; such as wound dressing, tissue engineering, drug delivery, and dental application. Numerous natural polymers have been investigated for the development of different drug delivery systems [2–4]. For this use, alginate was developed and applied in drug delivery systems in form of capsules, hydrogels, tablets, nanoparticles, beads, microspheres, films, membranes, and others [4–7].

In the process, the chapter focus on the alginate metal complex preparation, application of the prepared complexes, a comparison of the release behavior between different alginate metal complex loaded with two chiral drugs (Profens). This includes the effect of bead kind on the enantioselective release (ESR) and the release mechanism due to the chiral interaction between alginate complexes and chiral drugs. Finally, the case study section discusses ketoprofen-loaded beads preparation in the presence of two ion metal types and an In-vitro ESR study for the prepared beads during the experiment time. Therefore, this chapter summarizes our current thought about alginate metal complex application as an ESR agent in addition to its role in many other fields.

### **2. General properties of alginate**

Sodium alginate is the most common salt of alginic acid, it is a water-soluble and natural nontoxic polysaccharide extracted from marine brown algae. It contains 2

**Figure 1.**

*Chemical structure of alginate, A: alginate monomers, B: structures of G-block, M-block, and alternating block in alginate.*

uronic acids, β-D-mannuronic acid (M) and α-L-guluronic acid (G) [8], and it is composed of homopolymeric blocks MM or GG, and blocks with an alternating sequence (MG blocks) [9, 10], **Figure 1**. The alginate's rigidity decreases along with the series GG > MM > MG due to its different contents of M and G; which depends on alginates' different sources. On the other hand, the divalent metal ions affinities to alginate are dependent on the M: G units' ratio.

The alginate's affinity for divalent ions increases in the order [9]:

a.Alginate from *Laminaria digitata* rich with M units:

Pb > Cu > Cd > Ba > Sr > Ca > Co, Ni, Zn, Mn > Mg

b.Alginate from *Laminaria Hyperborea* rich with G units:

Pb > Cu > Ba > Sr > Cd > Ca > Co, Ni, Zn, Mn > Mg

The divalent cations concentration for complex formation from the two types of seaweeds is the same and follow the order:

Ba < Pb < Cu < Sr < Cd < Ca < Zn < Ni < Co < Mg.
