Sildenafil-Coated Silver Nanoparticles for Anal Fissure Wound Healing—A Combined Experimental/Molecular Docking Study

PVP-stabilized silver nanoparticles (Ag NPs) were functionalized with sildenafil (Sil), leading to spherical NPs (Ag@Sil NPs) with a size of about 30 nm as observed through transmission electron microscopy and dynamic light scattering. Fourier-transformed IR spectroscopy confirmed the covering of the particles with Sil. The Ag@Sil NPs were incorporated into a 0.1 wt% ointment and tested for the treatment of acute anal fissures in a preliminary medical study involving 50 patients. Typical symptoms such as pain, bleeding, itching, and mass sensation were improved in the intervention group with no adverse effects. Molecular docking showed strong interactions with docking scores slightly above −10 kcal/mol between sildenafil and two different model complexes [Ag–Sil]+ for the Ag-bound sildenafil with either piperazine-N- or pyrazole-N-bound Ag+ ions and the muscarinic M2 and the nicotinic acetylcholine α3β4 receptor, which are both involved in anal sphincter regulation. All three showed superior binding compared with nitroglycerin and L-arginine. The residue analysis revealed a higher number of relevant interactions for the sildenafil and the two Ag+ complexes, compared to nitroglycerin and L-arginine, fully in line with the differences in the docking scores.