Structural, Spectroscopic (NMR, IR, and Raman), and DFT Investigation of the Self-Assembled Nanostructure of Pravastatin-LDH (Layered Double Hydroxides) Systems

Abstract

Layered double hydroxide (LDH) nanocontainers, suitable as carriers for anionic drugs, were intercalated with Pravastatin drug using magnesium–aluminum and zinc–aluminum in a MII/Al molar ratio equal 2 and different Al3+/Pravastatin molar ratios. Postsynthesis treatments were used in order to increase the materials crystallinity. Hybrid materials were characterized by a set of physical chemical techniques: chemical elemental analysis, X-ray diffraction (XRD), mass coupled thermal analyses, vibrational infrared and Raman spectroscopies, and solid-state 13C nuclear magnetic resonance (NMR). Results were interpreted in light of computational density functional theory (DFT) calculations performed for Sodium Pravastatin in order to assign the data obtained for the LDH intercalated materials. XRD peaks of LDH-Pravastatin material and the one-dimensional (1D) electron density map pointed out to a bilayer arrangement of Pravastatin in the interlayer region, where its associated carboxylate and vicinal hydroxyl groups are close to the positive LDH. The structural organization observed for the stacked assembly containing the unsymmetrical and bulky monoanion Pravastatin and LDH seems to be promoted by a self-assembling process, in which local interactions are maximized and chloride ion cointercalation is required. It is observed a high similarity among vibrational and 13C NMR spectra of Na-Pravastatin and LDH-Pravastatin materials. Those features indicate that the intercalation preserves the drug structural integrity. Spectroscopic techniques corroborate the nature of the guest species and their arrangement between the inorganic layers. Changes related to carboxylate, alcohol, and olefinic moieties are observed in both vibrational Raman and 13C NMR spectra after the drug intercalation. Thus, Pravastatin ions are forced to be arranged as head to tail through intermolecular hydrogen bonding between adjacent organic species. The thermal decomposition profile of the hybrid samples is distinct of that one observed for Na-Pravastatin salt, however, with no visible increase in the thermal behavior when the organic anion is sequestrated within LDH gap.

Mg–Al and Zn–Al Layered Double Hydroxides Promote Dynamic Expression of Marker Genes in Osteogenic Differentiation by Modulating Mitogen‐Activated Protein Kinases

“…Considering the possibility of controlling the chemical composition of LDH layers and their affinity for anions, drugs, and other biological bioactive species, they have been confined between the inorganic layers for drug delivery and imaging . Our group has been studying experimental parameters for the intercalation of drugs such as pravastatin and sulindac into LDHs and applying structural, spectroscopic, textural, and thermal techniques for their detailed characterization . We recently reported the biological properties of a LDHs intercalated with the anion of mefenamic acid evaluated through the in vitro cytotoxicity tests by hemolysis, and in vivo tests concerning the anti‐inflammatory activity and nociceptive effect of the intercalated and nonintercalated drug .…”

Delivery system for mefenamic acid based on the nanocarrier layered double hydroxide: Physicochemical characterization and evaluation of anti-inflammatory and antinociceptive potential

“…The LDHs materials (LDH-Mef and LDH-Cl) were synthesized by coprecipitation method as described in the literature [27,28]. The hybrid LDH-Mef sample was obtained using the Mg 2+ /Al 3+ molar ratio equal to 2 and mefenamate/Al 3+ equal to 1.…”

“…The layer charge density of LDH with Mg/Al molar ratio equal 2 is around 25 Å 2 /electric charge, [27] whereas mefenamate monoanion displays an area of 60 Å 2 (9.00 Å × 6.65 Å), projected on the inorganic sheet, when intercalated perpendicularly, to maximize the interactions between the carboxylate group and the positive layers. Thus, it can be seen that mefenamate monoanion is too large and unable to compensate one LDH positive charge.…”

“…In order to suggest an arrangement for the mefenamate interdigitated bilayer, the disposition of the free mefenamic acid molecule in its crystal was taken into account, since we have observed that the pravastatin drug orientation between LDH layers (determined by 1D plot) is in close relation to its packing in the pravastatin tert-octyl ammonium salt [27]. Mefenamic acid exists as a dimer in the solid state and adjacent pairs of molecules interact through the dimethylphenyl rings, Fig.…”

Materiais à base de hidróxidos duplos lamelares de cobalto e alumínio: intercalação, reatividade e formação de compósitos por pirólise

“…As amostras em estado sólido foram acondicionadas em tubos de polipropileno e os espectros obtidos à temperatura ambiente. A síntese foi finalizada após cerca de 3 horas, devido à lenta adição da solução de cátions e adição contrabalanceada de NaOH, na qual a variação no 74 valor do pH manteve-se em ± 0,1. A coloração da suspensão resultante foi "rosa quente", concordante com a literatura [71,73].…”