# Mucoadhesive Hydrogel Nanoparticles as Smart Biomedical Drug Delivery System
## 6 Mucoadhesion and Its Relation with Certain Polymers
The cause of this dissolution is related to the pKa of its carboxyl group, i.e., at low pH it is protonated and the polymer is insoluble, while it is deprotonated at higher pH leading to polymer dissolution [52]. It is reported that the combination of PgA with a second polymer into a composite may alter the degree of swelling and can change its mechanical properties [53], improving both the stability of encapsulated drugs and the control of their release. \begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Polymer** & **Chemical Structure** & **Charge** & **Hydrogel Groups** & **Structure** \\ \hline Chitosan & Poly[\(\beta\)-(1,4)-2-amino-2-deoxy-D-glucopyranoside] & Cationic & NH\({}_{2}\) and OH & \\ \hline Hyaluronic acid & D-glucuronic acid and N-acetyl–D-glucosamine linked together through alternating \(\beta\)(1,3) and \(\beta\)(1,4) glycosidic bonds & Anionic & COOH and OH & \\ \hline Alginic acid & \(\beta\)-(1,4)-D-mannuronic acid (M) and \(\alpha\)-(1,4)-L-galuronic acid (G) units & Anionic & COOH and OH & \\ \hline Polygalacturonic acid & Heterogeneous structure bonded via \(\alpha\) (1,4) glycosidic linkage. & Anionic & COOH and OH & \\ \hline Carboxymethyl cellulose & Cellulose derivatives & Anionic & COOH and OH & \\ \hline Poly(acrylic acid) & Polyacrylates & Anionic & COOH and OH & \\ \hline \hline \end{tabular}
\end{table} 
Table 3: Polymers used to optimize mucoadhesive systems. It is reported that the addition of pectin to mucin in deionized water can form an aggregated compound, demonstrating an association between pectin and mucin [54]. Despite both polymers bearing a negative charge, this reaction probably induces a hydrogen-molecular interaction, where electrostatic repulsion may cause the uncoiling of polymer chains, facilitating chain entanglement and bond formation [55]. Poly(acrylic acid) (PAA) is a hydrophilic polymer [56] that adopts a random coil conformation in solution. In their recent work, [PERSON] and his colleagues have further demonstrated that these coils have swelling properties under certain ionic strengths and salt concentrations, leading to extended chain conformations in alkaline solutions (Figure 4) [49; 57; 58; 59]. This is due to the COOH side chain which is pH responsive, i.e., protonated (COOH) at pH \(\leq\) 5 while de-protonated (COO-) at pH \(>\) 5 [60]. In aqueous media of appropriate pH and ionic strength, the carboxylic groups ionize and develop fixed charges on the polymer network, generating electrostatic repulsive forces responsible for pH-dependent behavior, causing swelling or shrinking of the hydrogel structure [61]. PAA is expected to form a hydrophilic corona. While in alkaline pH, the interaction of the swelling coils of PAA with water makes it more favorable for protection, as it adsorbs water at a weight many more times than that of its own. [62; 63]. Additionally, PAA is poorly soluble in water at low pH, causing structure shrinkage. This mechanical elasticity is predicted to protect the micelles during oral administration and through the gastrointestinal tract. Poly(acrylic acid) doped with cysteine can increase mucus glycoprotein adhesion via thiol-disulfide reaction. This reaction can significantly improve the mucoadhesive properties of PAA [64]. Carboxymethyl cellulose (CMC) is a biodegradable polymer and a cellulose derivative. CMC is a good candidate for hydrogel formation because it has a good swelling capacity. Its carboxyl and hydroxyl groups are mainly responsible for hydrogel assembly due to their hydrogen intramolecular reaction [65]. [PERSON] and his colleagues fabricated a hydrogel system upon a surface of fluoro-magnetic  
Figure 4: Poly(acrylic acid)extended at alkaline condition and shrunk at acidic condition(figure adapted from [49] and [56]). Figure 3: Dissolution of PgA by alkaline solution (figure adapted from [49]). nanoparticles by using polyethylene glycol and carboxymethyl cellulose. This hydrogel was constructed using layer-by-layer assembled polymers.