# Alginate Modification and Lectin-Conjugation Approach to Synthesize the Mucoadhesive Matrix
## 5 Lectin-ADA Conjugation
### Lectin-Alginate Dialdehyde Conjugate  
Carbodiimide chemistry is a popular method of crosslinking a macromolecular carrier with lectins. Previous studies agree that the process is non-destructive toward the bioadhesion of lectins [8]. This method is favored because it can maintain the bioactivity of  
\begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Carrier** & **Lectin** & **Glycan Preference** & \multicolumn{2}{c}{**Carrier-Lectin**} & \multicolumn{1}{c}{**Targeted Cell/Organ**} & **Ref. ** \\ \hline  & & & & & Caco-2 cells \\  & & & & & Caco-2 and HT-29 cells \\ PLGA nanoparticles & Wheat germ agglutinin & Siallic acid and N-acetyl & & & (colon cancer) \\  & (WGA) & glucosamine (GlcNAcNac) & & & 849 cells (Type II alveolar epithelial cells) \\  & & & & & Wistar rats \\ PLGA nanoparticles containing & Wheat germ agglutinin & Siallic acid and N-acetyl & & & A549 cells, HI299 cells \\ isopropyl myristate (IPM) & Wheat germ agglutinin & Siallic acid and N-acetyl & & & (non-small cell lung carcinoma), CC-18 cells \\ Carboxymethylal & Wheat germ agglutinin & Siallic acid and N-acetyl & & & (lung fibroblast IMR-90) \\ kappa-carrageenan & & & & & \\ microparticles & & & & & \\ Poly-t-glutamic acid (TGA) and & Wheat germ agglutinin & Siallic acid and N-acetyl & & & \\ \(\alpha\)-poly-(1-)glutamic acid (TGA) & (WGA) & glucosamine (GlcNAc) & & & \\ Methoxy polyethylene & & & & & \\ glycol)-poly-(expolactic) & & & & & \\ (MPEG-PCL) nanoparticles & & & & & \\ Tholated alginate nanoparticles & & & & & \\ Chitosan-Ca-aliginate & Wheat germ agglutinin & Siallic acid and N-acetyl & & & \\ (CTS-Ca-ALG) microparticles & & & & & \\ Wheat germ agglutinin & & & & & \\ Liposomes & Wheat germ agglutinin & Siallic acid and N-acetyl & & & \\  & (WGA) & glucosamine (GlcNAc) & & & \\  & & & & & \\  & & & & & \\  & & & & \\  & & & & & \\ Liposomes & & & & & \\  & & & & \\  & & & & \\  & & & & & \\ Liposomes nanocarriers & agglutinin (WGA), and & & & \\  & & & & \\  & & & & \\  & & & & \\ Glyadin nanoparticle (PAL) microspheres & & & & & \\  & & & & \\ Poly(lactide) (PLA) microspheres & & escelintum agglutulin  
substrates. However, carbodimide is associated with urea derivatives formation, which leads to the destruction of the hydrogel properties of alignates [38]. Crosslinking strategies involving polysaccharides, alginate in particular, usually start with two or more steps. The first step is to provide the biopolymer with sufficiently reactive groups. In these cases, periodate oxidation is one way to create these groups. With access to controlling the degree of oxidation, this method creates highly reactive aldehyde functionalities. By using a proper amount of periodate, a sufficient number of aldehydes will be obtained without losing the desired characteristic of alignates. The resulting biopolymer is known as alginate dialdehyde (ADA) and can be used in coupling reactions with amine-containing molecules, in this case, lectins. Covalent linkages are expected to form after amines react with formyl groups under reductive amination conditions using a suitable reducing agent. The two-step modification reactions, periodate oxidation and reductive amination, are used to synthesize alginate-derived surfactants [130]. The polymeric surfactants consist of alginate dialdehyde coupled with a linear alkyl amine in the presence of sodium cyanoborohydride. By using a mild reduction agent, \(\alpha\)-picoline borane, two studies generate a functional alginate dialdehyde. The first study coupled one model molecule, \(\lambda\)-Tyrosine methyl ester, to determine the optimum coupling condition, and reached between 2-6% degree of substitutions [67]. This optimum condition was then applied to the ADA by coupling three different bioactive peptides (GRGDSP, GRGDYP, and KHIFSDDSSE) with an 8% degree of oxidation and substitution range from 3-6%. The dental stem cells (RP89) and myoblasts (C2C12) were used for cell adhesion studies, and they demonstrated the bioactivity of GRGDSP.