βCD-based nanosponges vs. nigerose-based NS: piroxicam inclusion vs. adsorption and self-aggregation via molecular dynamics simulations

β-cyclodextrins (βCDs) cross-linked with pyromellitic dianhydride (PMA) form 3D nanoporous polymers called cyclodextrin nanosponges (CDNS) able to encapsulate hydrophobic and lipophilic drugs [1]. Cyclic nigerosyl-1,6-nigerose (CNN) [2] is an interesting monomer that cross-linked with pyromellitic dianhydride form a polymer without cyclic hydrophobic cavities as shown by βCDNSs. Synthetized by Trotta et al [2] CNN is able to solubilize hydrophobic drugs for their release [2] such as PMA βCDNS as experimentally studied by Pivato et al. [3]. In the present theoretical work molecular mechanics (MM) and molecular dynamics (MD) simulations at the atomistic level [4] are performed to understand the intermolecular interactions between piroxicam ― an efficient nonsteroidal anti-inflammatory agent widely used for the treatment of pain in musculoskeletal disorders ― and both a PMA βCDNS and CNN. Drug encapsulation occurs only in βCD cavities in PMA βCDNS. In both cases, the drug adsorption and self-aggregation process on the surface exposed by the carrier take place. Different drug-carrier geometries of interaction and different strength of the intermolecular interactions could explain the different diffusion [4], in two steps or in single step, as found in NMR experiments [3].