# Alginate Modification and Lectin-Conjugation Approach to Synthesize the Mucoadhesive Matrix
## 1 Introduction  
Alginates are examples of anionic polymers obtained from brown seaweed. To date, alignates have been used in numerous biomedical applications due to their biocompatibility, low toxicity, and abundant sources. Alginates are attractive for wound healing, tissue engineering, and drug delivery applications and have become more favored because of their hydrogel formation ability in mild conditions [1, 2]. Because of their well-known advantages, the recent trend of added-value alignates is rising. Functionalization is a potential way to generate alginate derivatives and gives new additional properties to the biopolymer. The functionalization has provided the possibility to form ionic and covalent crosslinking. They result in improved physical and chemical properties and additional biological activity, thus factually accommodating the proposed application demand. Alginate derivatives can be synthesized through chemical modifications, including esterification, amidation, acetylation, phosphorylation, sulfation, graft copolymerization, and oxidation and reduction [3]. On the other hand, lectins have earned drug targeting researchers' attention as they provide target specificity [4]. They are known as proteins that can recognize and bind to specific sugar complexes attached to proteins and lipids. These bindings are supported by the carbohydrate recognition domain (CRD) within the structure [5]. Additionally, the binding specificity and endocytosis of lectins depended on that structure. One study has suggested that lectins be coupled with macromolecular carriers, allowing cellular uptake and controlled intercellular route [6]. The adhesivity of lectin wheat germ agglutinin (WGA) coupled with a model drug, fluorescent bovine serum albumin (FBSA), is investigated, and glycine-FBSA is used as a control [7]. The WGA is managed to increase the interaction withCaco-2 single cell 2-8 times higher than glycine. The cell adhesion specificity corresponds to the amount of WGA and the molecular size of the formed WGA-FBSA coupled polymer. In the subsequent report, WGA is occupied as the targeting moiety for poly(lactic-co-glycolic acid) (PLGA) microparticle loaded with three fluorescent model drugs; fluorescein sodium, sulforthodamine, and boron-dipyrromethene [8]. The crosslinking between PLGA and WGA is established with carbodimide chemistry, and the binding rate of WGA-PLGA is recorded as having up to a 3-fold increase compared to the non-grafted PLGA. The mucoadhesive property in drug delivery is to localize and prolong an active ingredient at a particular site in the body. Extending the contact time of the delivered active ingredients will improve the poor adsorption drug's bioavailability, increasing the therapy's effectiveness. Both alginate and lectin show adhesiveness characteristics. These biopolymers could perform interfacial interactions with mucus membranes (e.g., gastrointestinal, buccal, nasal, etc. ), especially for lectin; its specific adhesivity is based on its glycan preference. Additionally, the mucoadhesive ability depends on the nature of the mucosal tissue and the physicochemical properties of the polymeric drug delivery formulation [9]. One of the goals to be achieved from alginate functionalization is to enhance chemical interaction with cells through mucoadhesion. Studies show that the low affinity of alginate matrices can be boosted with an attachment of cell targeting or signaling moieties [1]. With their bioadhesive properties, lectins are proposed as a targeting media in drug delivery [10]. Together with lectins, alginates could form molecules with an improved acidic and enzymatic degradation resistance, making them suitable for oral delivery. Hence, a particular set of alginate characteristics is often required to perform well in a specific application. Thus, chemical modification is one helpful way to fulfill the necessity. Here we report the strategies to functionalize the alginate biopolymer based on available functional groups and the following conjunction of mucoadhesive moieties.