# Cationic Moieties in Polystyrene Gels Swollen with D-Limonene Improved Transdermal Delivery System
## 3 Results and Discussion
### Swelling Behavior and Rheological Property of PS Gels Swollen in Limonene  
All gels were prepared directly by polymerization in d-limonene as solvent due to the good solubility of St in limonene [19; 20]. Swelling ratios of various compositions of gels were determined as shown in Figure 2. The cross-linker amount of PS gel was compared at DVB contents of 5 and 10 mol % to evaluate the effect of the cross-linking degree on the density of the network structure and swelling properties. The swelling degree was decreasing as expected upon increasing the amount of cross-linker from 4.5 and 2.9 for 5 and 10 mol %, respectively (Figure 2a,b). These results confirmed the formation of a denser network structure when the cross-linking degree of PS gel was increased. Furthermore, the swelling ratio of PS-4 VP gel (gel F-J in Figure 2c-g) and PS-VBAC gel (gel K and L in Figure 2h,i) with 5 mol % cross-linker were determined. The swelling ratios of PS-4 VP gels were not significantly affected by enhancing of 4 VP ratio in a range of 2-3 mol % (Table 1, entries 6-8), illustrating a swelling ratio of about 2.9 (Figure 2c-e). However, the swelling ratio of 4 and 5 mol % (Table 1, entries 9 and 10) of 4 VP (gel I and J) were slightly decreased to2.68 and 2.43, respectively (Figure 2f,g). The shrinkage of gel I and J was caused by the low solubility of 4 VP in d-limonene. In the same way, the VBAC was introduced at only 0.5 and 1 mol % (Table 1, entries 11 and 12). Their swelling ratio was calculated as 2.68 and 2.34, respectively (Figure 2h,i). As a result, the swelling ratio of PS gel was about 1.5 time higher for the cationic gels as PS-4 VP gel and PS-VBAC gel which were referred to limitation of solubility in limonene. Previously, the rheological analyses on PS gels has been reported [20]. In this study, we further investigated the rheological properties with the detailed crosslinking and comonomer's ratios regarding the PS gels obtained in d-limonene (Figure 3). The elastic modulus (G') of gel B (Figure 3b) showed higher than that of gel A (Figure 3a), based on the higher crosslinking degree under 4 M condition. The same tendency was recognized between gel D (Figure 3d) and gel C (Figure 3c) under 8 M condition. Gel D illustrated the most rigid network structure providing an elastic modulus of 98 kPa at a frequency of 1 Hz (Figure 3d). This is about 2 times higher than gel C of 44 kPa (Figure 3c) and about 6 times higher than gel B of 6.7 kPa (Figure 3b). On the other hand, the concentration of the gel effects the strength of the network structure more than the cross-linking control as indicated by the elastic modulus. It is shown that elastic moduli of the cationic gels, PS-4 VP gel as gel F-J from 2-5 mol %-4 VP (Figure 3f-j) and PS-VBAC gel as gel K and M between 0.5-1 mol %-VBAC (Figure 3k,l). The addition of 2% 4 VP improved the elastic modulus from 680 Pa to 2600 Pa, when gel A and gel F were compared (Figure 3a,f). While the amount of 4 VP in gel increased from 2 to 4 mol % (Table 1, entries 6-9), the G' value gradually increased from 2600 Pa to 21 kPa (Figure 3f-i). However, the increasing ratio of 4-vinylpyridine until 5 mol % (Table 1, entry 10), the elastic modulus dropped from gel I which is 21 kPa to 14 kPa (Figure 3j). These results suggest that there is an optimized value for the strongest composition due to the complicated factors, such as electrostatic repulsion and the composition of monomers. Correspondingly, introducing a higher ratio of VBAC resulted in a lower elastic modulus in PS-VBAC gel (Table 1, entries 11 and 12), resulting from stronger repulsive forces of positively charged ammonium making the gel softer (Figure 3k,l). After the evaluation of mechanical strength, the influence of the cationic moieties in the gel-drug interaction were evaluated. The intermolecular interaction was observed by FT-IR spectra. The 4 VP contained C-N aromatic bond appeared at 1281 cm\({}^{-1}\) while ibuprofen has C=O from carboxylic group at 1711 cm\({}^{-1}\) (Supporting Information, Figure S3).