## 3 Results and Discussion
### Drug-Polymer Interaction
The other interactions are pi-alkyl between the carbon atom and the second aromatic ring, between the last carbon atom and the second aromatic ring, and between the same atom and the molecule's central region. Figure 9B shows the interaction between PCL and QPhNO\({}_{2}\). Four favorable interactions were identified: one pi-sigma bond (hydrophobic interaction) between a carbon atom and an aromatic ring and three pi-alkyl bonds (hydrophobic interaction) between the molecule's center and carbon atoms in the aromatic rings. Lastly, Figure 9C depicts the interaction between PLGA and QPhNO\({}_{2}\). This is the weakest interaction among all polymers studied. A conventional hydrogen bond is observed between the PLGA hydrogen atom and the double-bonded oxygen, a pi-donor-type bond between hydrogen and the aromatic ring, and a pi-alkyl bond between a carbon atom and the aromatic ring. It is known that pi interactions generally contribute to inhibitor binding because they are not affected by solvation or desolvation processes. Therefore, changes in the enthalpy/entropy ratio on free binding energy may be minimal. Additionally, we observe unfavorable bonds between the oxygen of the PLGA and the steric group of the QPhNO\({}_{2}\). As observed, both polymers of the QPhNO\({}_{2}\) molecule exhibited high lipophilicity, which hindered the medication delivery process. Lipophilicity refers to a compound's ability to dissolve in fats, oils, lipids, and non-polar solvents. In drug discovery, LogP is widely used as a quantitative measure of lipophilicity, offering insights into parameters such as solubility, cellular permeability, plasma protein binding, and metabolic stability [54; 55; 56]. These properties are essential for understanding the interaction behavior of drug molecules with polymeric matrices, directly influencing encapsulation efficiency and drug release profiles. The purpose of encapsulation is to protect the drug molecule so that it can reach the target tissue. However, to facilitate this delivery process, a surfactant solution, such as Tween(r) 80 (also known as Polysorbate 80), is often added after preparing the polymer and drug solutions. The surfactant helps improve the in vitro dissolution of the drug in water, thereby accelerating the release process and simulating an in vivo administration. Therefore, taking into account how the surfactant interacts with the (polymer + QPhNO\({}_{2}\)) system will help understand the drug delivery dynamics. Figure 10 shows our best simulations of Tween(r) 80 with the models of Figure 9. The results show that Tween(r) 80 interacts preferentially with the polymeric matrix in all three cases, avoiding interacting with QPhNO\({}_{2}\). Furthermore, minimal interaction was observed between the surfactant and the polymers, as described below: (PMMA + QPhNO\({}_{2}\))/Tween(r) 80: \(-\)0.392426 kcal/mol, (PCL + QPhNO\({}_{2}\))/Tween(r) 80: \(-\)0.383648 kcal/mol, and (PLGA + QPhNO\({}_{2}\))/Tween(r) 80: \(-\)0.31488 kcal/mol, indicating very weak interactions, especially in comparison with the polymer/drug interaction. Thus, although there is surfactant in the nanocapsule, it does not substantially interfere with the drug delivery process. These findings suggest that the molecules interact favorably for binding, with the most effective interaction occurring between QPhNO\({}_{2}\) and PCL, followed by the interaction between QPhNO\({}_{2}\) and PMMA, and the weakest between QPhNO\({}_{2}\) and PLGA. As a result, it is possible to tune the release mechanism according to the specific application of the drug, taking into account factors such as pH, temperature, ionic strength, and other environmental conditions in which it will be applied. In this study, the polymers were maintained as rigid structures, while the molecule (ligand) was considered a flexible structure.