## 3 Results and Discussion
### Drug Loading and In Vitro Release Studies  
Amoxicillin (AM) was chosen as a model drug because it is frequently used to treat degenerative disc disease or other related disorders; moreover, the injectable polymers loaded with AM can be used for the treatment of such diseases. The incorporation of AM in Plx-\(g\)-CMP hydrogel was performed by solubilization of the drug in the polymeric solution at a low temperature followed by its gelation at the temperature of 37 \({}^{\circ}\)C. In this way, the entire amount of drug is retained in the hydrogel, having a uniform distribution within  
Figure 6: Self-healing test for the hydrogel containing 13% (\(w/v\)) Plx-\(g\)-CMP by following the evolution of the viscoelastic parameters in time, when two successive levels of deformations were applied each for 200 s: 1% and 100% (37 \({}^{\circ}\)C, 1 rad/s). the three-dimensional matrix. In fact, the polymer has an anionic charge and hydrophobic pendant chains, therefore, it can interact with both charged and hydrophobic drugs. The release studies of the AM from the hydrogel obtained at two polymer concentrations (13 and 22%, \(w/v\)) were performed under simulated physiological conditions (PB at pH = 7.4) (Figure 7). A gradual release of AM from both hydrogels over a period of about 168 h can be observed. Within the first 6 h, 41% of the drug is released from Plx-g-CMP hydrogel obtained at a concentration of 13% (\(w/v\)), which is twice than that of the amount of drug released from the hydrogel obtained at a concentration of 22% (\(w/v\)). For the next 48 h, the release profiles follow almost the same pattern but the difference is lower. From this point and until the end of the study, the profile of the release curves follows an approximately parallel trajectory, suggesting that the diffusion of the drug is the rate-determining step. However, the diffusion of AM from the hydrogel to the release fluid should be controlled both by steric interactions with the polymer network and by the possible electrostatic interactions between an opposite charged drug/CMC. As long as release studies are performed in a phosphate buffer with a certain ionic strength (50 mM), the electrostatic interactions between the drug and carboxylic groups of CMP could be shielded by the presence of competing ions. As a result, the rate of drug diffusion will be controlled only by the steric interactions between the drug and the polymer network. Evidently, the denser the network, the higher the probability of intermolecular interactions and the lower the release rate. In order to further understand the in vitro drug release mechanism of AM, the experimental data were analyzed using the mathematical models described by Equations (3)-(6) (Figure 8). The results (Table 1) revealed that the in vitro release profile of AM in PB (pH 7.4) followed the Higuchi equation (low AIC value), and according to the Ritger-Peppas model, the drug release mechanism pointed out the prevalence of the diffusional mechanistic phenomena, since the values of the diffusional exponent \(n\) obtained were lower or close to the standard value for declaring Fickian release behavior (\(n\leq 0.45\)). Figure 7: In vitro release profiles of AM from Plx-g-CMP hydrogels obtained at two concentrations (13% and 22%, \(w/v\)). As shown in Table 1, the Peppas-Sahlin model possesses a lower AIC value than that of the Higuchi and Ritger-Peppas models, which indicates that the former was the more appropriate one to describe the release data than the latter (see Figure 7). These observations indicate that the drug release mechanism was a result of the contribution of Fickian diffusion and polymer chain relaxation. However, a negative value of \(k_{2}\) was obtained, which means that the relaxation process has a negligible effect on the AM release compared to the Fickian diffusion. For a hydrogel matrix that contains a molecularly dispersed diffusing drug, the apparent diffusion coefficient may be calculated by using the 1D unsteady-state form