Anionic Clays Containing Anti-Inflammatory Drug Molecules:  Comparison of Molecular Dynamics Simulation and Measurements

Abstract

Three representative nonsteroidal anti-inflammatory drug molecules, Ibuprofen, Diclofenac, and Indomethacin, have been intercalated within the galleries of an anionic clay, Mg-Al layered double hydroxide (LDH). X-ray diffraction, IR and Raman vibrational spectroscopy and (13)C cross-polarization magic-angle spinning NMR have been used to characterize the confined drug molecules, while molecular dynamics (MD) simulations were used to probe the interlayer structure, arrangement, orientation, and geometry of the intercalated species. All three drug molecules are arranged as bilayers in the interlamellar space of the anionic clay. But while the structure of the intercalated Ibuprofen is identical to that of the molecule outside the layers, spectroscopy as well as MD simulation shows that there is a change in the geometry of Diclofenac and Indomethacin upon confinement within the galleries of the LDH. The change in geometry of Diclofenac and Indomethacin upon intercalation is shown to originate from the electrostatic interaction between the electronegative chlorine atoms on the drug molecule and the positively charged metal hydroxide sheets of the anionic clay. It is shown that these changes in the geometry of the intercalated drug molecules allow for the observed interlayer spacing to be realized without the bilayers having to interdigitate, which would otherwise have been necessary if the structure of the drug molecules had remained identical to that outside the layers. Comparisons of experimental measurements with simulation have provided a more detailed understanding of the geometry and organization of flexible drug molecules confined in the anionic clay.

Praziquantel in a Clay Nanoformulation Shows More Bioavailability and Higher Efficacy against Murine Schistosoma mansoni Infection

“…On the other hand, inorganic clay nanomaterials were found to possess the privilege of accommodating drugs between their layers, forming a variety of intercalated compounds. The intercalation of organic species (e.g., PZQ) into layered inorganic solids provides a convenient route to prepare organic-inorganic hybrids that contain properties of both the inorganic host and the organic guest in a single material: high specific surface area, adsorptive capacity, rheological properties, chemical inertness, and low or null toxicity (37) and power to effectively modulate and control drug release from drug-intercalated layered materials (21,38).…”

Comparative study of Mg/Al- and Zn/Al-layered double hydroxide-perindopril erbumine nanocomposites for inhibition of angiotensin-converting enzyme

“…15 A solution of magnesium nitrate 0.025 mol/L and aluminum nitrate 0.0125 mol/L was prepared in deionized water. A solution of sodium hydroxide at a concentration of 2 mol/L was added dropwise to the mother liquor solution with vigorous stirring under a nitrogen atmosphere until a pH of 10 was reached.…”

“…The accumulated amount of perindopril released into the solution was measured at regular intervals using an ultraviolet-visible spectrophotometer at 215 nm. To compare the release rate of perindopril from PMAE with that from the physical mixture of perindopril and pristine Mg/Al-layered double hydroxide (prepared for this purpose), 18 0.6 mg of the physical mixture of perindopril (0.22 mg) and the pristine layered double hydroxide (0.38 mg) was also used to perform the same perindopril release experiments.…”

Adsorption of charged protein residues on an inorganic nanosheet: Computer simulation of LDH interaction with ion channel

“…The Mg/Al-LDH Nanosheet MD Models An LDH nanosheet having the chemical composition [Mg 4 A l2 (OH) 12 ] 2+ 2Cl -nH 2 O was chosen for the model. The structure was built using X-ray crystallographic data from Refs.…”

“…In recent decades inorganic twodimensional nanomaterials and bio-nanohybrids based on clay minerals have been employed for targeted drug and gene delivery with controlled release [4,5], medical imaging and protein separation [6], which is an intensively developing field in nanomedicine, diagnostics and pharmaceutics [7,8]. Hierarchical nanoparticles with an external shell made of layered hydroxides and oxyhydroxides of metals are used as multifunctional bioactive agents for biomedical purposes [9,10] including anti-cancer therapy [11,12].…”