Comparative binding effects of celecoxib/ poly(lactic-co-glycolic acid) microparticles with enhancing anti-inflammatory and anti-cancer activities: Density functional theory, molecular Docking, and ADMET calculations

This study is to evaluate the enhancement of anti-inflammatory and anti-cancer activities of celecoxib (CXB) in a dichloromethane (DCM) environment by poly(lactic-co-glycolic acid) (PLGA), using density functional dispersion correction (DFT-D), time-dependent density functional theory (TDDFT), molecular docking (MD), and ADMET calculations. The CXB, via its sulfonamide (-NH2SO2) group contact with the PLGA in state B through hydrogen bonds, is stronger than in states A and C, according to our computed analyses based on binding energy and chemical reactivity parameters. According to the theoretical analysis of IR spectra, the interaction of CXB with PLGA causes shifts in both the pure PLGA and the CXB. In the presence of stronger negative Gibbs free solvation energy (Gsolv) values, the CXB interaction with PLGA results in the increment of dipole moment, higher solubility, and the energy gap (Eg) reduction. Further, MD calculations on states A, B, and C were able to inhibit tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), cyclooxygenase-2 (COX-2), and human epidermal growth factor receptor 2 (HER2). Based on the MD calculations, the obtained data illustrated a strong interaction with the target binding pocket (CXB via the sulfonamide group interacting with PLGA in the state B), leading to the improvement of the anti-inflammatory and anti-cancer activities in comparison with the pure CXB.