Understanding Surface Interaction and Inclusion Complexes between Piroxicam and Native or Crosslinked β-Cyclodextrins: The Role of Drug Concentration

Abstract

Drug concentration plays an important role in the interaction with drug carriers affecting the kinetics of release process and toxicology effects. Cyclodextrins (CDs) can solubilize hydrophobic drugs in water enhancing their bioavailability. In this theoretical study based on molecular mechanics and molecular dynamics methods, the interactions between β-cyclodextrin and piroxicam, an important nonsteroidal anti-inflammatory drug, were investigated. At first, both host–guest complexes with native β-CD in the 1:1 and in 2:1 stoichiometry were considered without assuming any initial a priori inclusion: the resulting inclusion complexes were in good agreement with literature NMR data. The interaction between piroxicam and a β-CD nanosponge (NS) was then modeled at different concentrations. Two inclusion mechanisms were found. Moreover, piroxicam can interact with the external NS surface or with its crosslinkers, also forming one nanopore. At larger concentration, a nucleation process of drug aggregation induced by the first layer of adsorbed piroxicam molecules is observed. The flexibility of crosslinked β-CDs, which may be swollen or quite compact, changing the surface area accessible to drug molecules, and the dimension of the aggregate nucleated on the NS surface are important factors possibly affecting the kinetics of release, which shall be theoretically studied in more detail at specific concentrations.

Adsorption of Chiral [5]-Aza[5]helicenes on DNA Can Modify Its Hydrophilicity and Affect Its Chiral Architecture: A Molecular Dynamics Study

“…The competitive adsorption process on double-stranded DNA is reported adopting the same simulation protocols proposed in previous work on the theoretical study of non-covalent interactions in the formation of inclusion cyclodextrin complexes [27][28][29] and the adsorption of proteins on biomaterials surfaces influenced also by the topography, in particular the curvature of carbon nanotubes also having different chirality [30,31]. Furthermore, the competitive adsorption [32] and the self-aggregation process of systems that can spontaneously form aggregates [33] and the importance of drug concentration in nanocarriers devices [34] can be considered atomistically using MM and MD simulations. Using the same theoretical methods adopted in previous work, the aggregation of enantiopure compound or racemic mixture of 5-Aza [5]helicenes, at low and high concentrations, was also studied.…”

Inclusion Complexes Between β‐cyclodextrin and the Anticancer Drug 5‐Fluorouracil for its Solubilization: a Molecular Dynamics Study at Different Stoichiometries

“…[5][6][7][8] In the past, 20 years Molecular Mechanics (MM) and Molecular Dynamics (MD) simulations have demonstrated to be a powerful tool for atomistically studying the conformational properties of drug molecules, protein adsorption on biomaterial surfaces, the role of noncovalent interactions and drug concentration in the process of formation of the inclusion complexes, and the formation and stability of adducts characterized by weak interaction also on the external surface of CDs. [9][10][11][12] In literature, Di Donato et al [13] show how the complexations of 5-FU with 𝛼-CD or 𝛽-CD are able to determine a significant increase in the anticancer activity of this widely used drug. The use of simple docking methods confirm that stable inclusion complexes between 𝛼-CD and 𝛽-CD with 5-FU in a 1:1 stoichiometry are formed.…”

On the Interactions of Melatonin/β-Cyclodextrin Inclusion Complex: A Novel Approach Combining Efficient Semiempirical Extended Tight-Binding (xTB) Results with Ab Initio Methods

“…Previous studies investigated the formation of non-covalent complexes between a guest and β-cyclodextrin with different computational methods and at different levels of theory. These kinds of complexes have been computationally investigated since the end of the XX century, treated at the classical mechanics or semi-empirical level [ 18 , 28 , 29 , 30 , 31 ], usually used as a complementary tool to experimental techniques, such as NMR [ 26 , 32 , 33 , 34 , 35 , 36 ], fluorescence [ 37 ] and X-ray diffraction [ 35 , 36 ], depending on the nature of the guest molecule. More recently, DFT methods have become the method of choice in computational chemistry because, at a reasonable computational cost, they are able to provide accurate geometrical parameters, properties, such as IR spectra, and complexation energies for a wide variety of systems, including organic systems.…”