Synthesis and characterization of nanocapsules containing anti-inflammatory drugs: <i>in vitro</i> and <i>in silico</i> biological activity

Cancer constitutes a major cause of death globally. Many current treatments are not very selective and often harm healthy cells. Inflammation is known to be associated with tumor growth, yet anti-inflammatory drugs alone are rarely used in a targeted manner. The aim of this study was to examine the synergic activity of two frequently used anti-inflammatory drugs, dexamethasone acetate (DA), and nimesulide (NIME) in nanoencapsulated form to diminish toxicity but enhance therapeutic effectiveness. The stability of the nanocapsules was established by applying light scattering, zeta potential, electron microscopy, and HPLC-DAD. The nanocapsules remained intact over time and exhibited a porosity and regular even shape, ideal for slow drug release. The encapsulated drugs initiated less harm to healthy HaCaT and L929 cells maintaining activity against cancer cells (HeLa, A375). Docking tests indicated that DA was bound effectively to the MMP-13/TIMP-2 complex, indicative of potential anti-inflammatory and anticancer effects. Molecular docking analysis noted that DA exhibited a stronger binding affinity to the target protein compared to NIME (binding energy: -8.7 kcal/mol, Ki: 0.423 µM vs. NIME: -6.8 kcal/mol, Ki: 10.4 µM), indicating a higher propensity for interaction. Further, DFT analysis demonstrated that NIME possessed a smaller HOMO - LUMO gap (0.132 eV), suggesting greater chemical reactivity, whereas DA exhibited a larger gap (2.806 eV), indicative of enhanced molecular stability. Computational results suggested that NIME was more reactive, while DA was more stable. Data suggest that nanocapsules may diminish side effects without reducing the benefits of these drugs against tumors.