# Cationic Moieties in Polystyrene Gels Swollen with D-Limonene Improved Transdermal Delivery System
## 3 Results and Discussion  
### Synthesis and Characterization of Limonene Organogels  
The limonene gels, poly(styrene-_co_-divinylbenzene) (PS gel), poly(styrene-_co_-divinylbenzene-_co_-4-vinylpyridine) (PS-4 VP gel) and poly(styrene-_co_-divinylbenzene-_co_-(vinylbenzyll) trimethylammonium chloride) (PS-VBAC gel) were prepared in d-limonene via radical polymerization (Figure 1a,b). The prepared gels in this study were listed in Table 1. The PS gels were prepared by varying the cross-linker ratio between 5 and 10 mol % and the concentration of d-limonene between 4 and 8 M resulting in gel A-D (Table 1, entries 1-4). These gels were used to study the effect of the network density. As a comparison, the PS gel was prepared in toluene as solvent for gel E (Table 1, entry 5). Moreover, the 4 VP which acts as cationic moiety was introduced at 2-5 mol % being PS-4 VP gel in gel F-J (Table 1, entries 6-10). As the other cationic moiety, the VBAC was introduced 0.5 and 1 mol % being PS-VBAC gel in gel K and L (Table 1, entries 11 and 12). Their elastic modulus (G') were also listed in Table 1. The existence of cationic moieties was verified by FT-IR spectra of dry gels in Figure 1c. The PS-4 VP gel, bearing pyridine group, was shown characteristic of C-N aromatic stretching at 1221 cm\({}^{-1}\) and C-N stretching at 1065 cm\({}^{-1}\). The PS-VBAC gel contained trimethyl ammonium group illustrated C-N stretching at 1053 and 1155 cm\({}^{-1}\).  
The 4 VP and VBAC served as interaction unit in the copolymer for the controlled release by interacting with the drug. The positively charged VBAC would be expected to show stronger interaction with ibuprofen than 4 VP (Figure S2). According to the interaction between drug and polymer chain, it could release ibuprofen through the skin in a controlled manner.  
\begin{table}
\begin{tabular}{c c c c c c c c} \hline \hline \multirow{2}{*}{**Entry**} & \multirow{2}{*}{**Sample**} & \multirow{2}{*}{**Gel Type**} & \multicolumn{2}{c}{**Ratio of**} & \multirow{2}{*}{**Cononomer**} & \multirow{2}{*}{**Cononomer**} & \multirow{2}{*}{**Cononomer**} & \multirow{2}{*}{**Con. (M)**} & \multirow{2}{*}{**G’ (Pa)**} \\  & & & & **(n: m:p) a** & & & & \\ \hline
1 & Gel A & & 95:5:0 & - & - & 4 & 680 \\
2 & Gel B & & 90:10:0 & - & - & 4 & 6800 \\
3 & Gel C & PS gel & 95:5:0 & - & - & 8 & 44,200 \\
4 & Gel D & & 90:10:0 & - & - & 8 & 98,600 \\
5 & Gel E b & & 95:5:0 & - & - & 4 & 1600 \\ \hline
6 & Gel F & & 95:5:2 & 4 VP & 2 & 4 & 2600 \\
7 & Gel G & & 95:5:2 & 4 VP & 2.5 & 4 & 10,300 \\
8 & Gel H & PS-4 VP gel & 95:5:3 & 4 VP & 3 & 4 & 11,700 \\
9 & Gel I & & 95:5:4 & 4 VP & 4 & 4 & 21,300 \\
10 & Gel J & & 95:5:5 & 4 VP & 5 & 4 & 14,000 \\ \hline
11 & Gel K & PS-VBAC & 95:5:0.5 & VBAC & 0.5 & 4 & 5000 \\
12 & Gel L & gel & 95:5:1 & VBAC & 1 & 4 & 1400 \\ \hline \hline \end{tabular}  
* the n, m and p are referred to the feeding ratio of St, DVB and SD (4 VP and VBAC), respectively from PS\({}_{n}\)-DVB\({}_{n}\)-SD\({}_{p}\) formulation. b Gel E was polymerized in toluene, while all the other gels were polymerized in limone.  
\end{table}
Table 1: Gel preparation and elastic modulus (G’).  
Figure 1: (**a**) Preparation of cross-linked PS gel in d-limonene. (**b**) Chemical structure of cross-linked PS gels. (**c**) FT-IR spectra of dry PS gel, PS-4 VP gel and PS-VBAC.