Síntese e caracterização de complexos farmacêuticos baseados em Hidróxido Duplo Lamelar (HDL) intercalado com nimesulida e ácidos graxos saturados e insaturados

Abstract

Nimesulide is a non-steroidal drug (NSAID) and presents biological activity based on the inhibition of the enzyme Cyclooxygenase-2 (COX-2) during the inflammation process. However, in the long term, the use of this drug can cause serious gastric disorders, in addition to high toxicity in normal tissues. To mitigate these possible effects, and thinking specifically for the Amazon region, other molecules with non-steroidal properties have been sought, from Amazonian oils. Among them are the fatty acids (saturated and unsaturated) that can be obtained from Amazonian oils. In addition, controlled drug release systems have been another alternative to mitigate side effects, in addition to increasing bioavailability, allowing effective dosages to remain in the bloodstream for a longer period of time, thus reducing the number of drug administrations to the patient. In these systems, the release rate of the active principle occurs from the matrix that transports it to its biological target. Within this context, there is the hybrid matrix of double hydroxide layered (HDL), obtained by the coprecipitation method. For these reasons, in this research, nimesulide was compared with the properties of some isolated saturated and unsaturated fatty acids. The comparison was based on molecular docking studies, using fatty acid molecules as potential COX-2 inhibitors. The best results found for fatty acids were intercalated in HDL as well as nimesulide, seeking to evaluate from its structural (DRX), vibrational (RAMAN) and morphological (SEM and SEM-FEG) characterizations the structuralmolecular mechanism of action of selected fatty acids as possible anti-inflammatory agents. The results demonstrate the direct influence of saturation on the intercalation of fatty acids in the HDL matrix. Among the complexes obtained, HDL-myristic acid presented a structural performance similar to that of HDL-nimesulide. And based on all the experimental and theoretical results obtained, three new and unprecedented complexes are proposed: HDLNimesulide, HDL-myristic acid and HDL-linoleic acid as potential anti-inflammatory agents that need to be investigated in in vitro tests.