Anti-Inflammatory and Analgesic Evaluation of a Phytochemical Intercalated into Layered Double Hydroxide

Abstract

Coumaric acid (CouH), an antioxidant molecule assimilated by food consumption, was intercalated into layered double hydroxide (LDH) nanocarrier, having zinc and aluminium ions in the layers (LDH-Cou), to evaluate its pharmacological activity through in vitro and in vivo assays in mice. Therefore, the following tests were performed: coumarate delivery in saline solution, fibroblasts’ cell viability using neutral red, peritonitis induced by carrageenan, formalin test, acetic-acid-induced writhing, and tail-flick assay, for the non-intercalated CouH and the intercalated LDH-Cou system. Furthermore, different pharmacological pathways were also investigated to evaluate their possible anti-inflammatory and antinociceptive mechanisms of action, in comparison to traditionally used agents (morphine, naloxone, caffeine, and indomethacin). The LDH-Cou drug delivery system showed more pronounced anti-inflammatory effect than CouH but not more than that evoked by the classic non-steroidal anti-inflammatory drug (NSAID) indomethacin. For the analgesic effect, according to the tail-flick test, the treatment with LDH-Cou expressively increased the analgesia duration (p < 0.001) by approximately 1.7–1.8 times compared to CouH or indomethacin. Thus, the results pointed out that the LDH-Cou system induced in vivo analgesic and anti-inflammatory activities and possibly uses similar mechanisms to that observed for classic NSAIDs, such as indomethacin.

Biomaterials Based on Organic Polymers and Layered Double Hydroxides Nanocomposites: Drug Delivery and Tissue Engineering

“…[ 22 , 24 ], vitamins (vitamin C, folic etc.) [ 107 , 108 ], phytochemicals (curcumin, coumaric, abietic, norbixin) [ 109 , 110 , 111 , 112 ], and nucleotides (DNA and RNA) [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ], as represented in Figure 8 . Hence, by combining different metal cations, stoichiometries and intercalated species, a huge number of LDH materials can be engendered to attend to pharmaceutical and medical needs.…”

“…The LC of LDH compounds is related to the amount of trivalent ion in the layers (the x value in the general formula [M 2+ (1- x ) M 3+ x (OH) 2 ](A n − ) x/n ), and with the electric charge of intercalated anions (the n value in the general formula). Considering both parameters, loading capacities of 30–50% can be reached [ 110 , 111 , 146 ]. However, the size/area of the anion can preclude the total neutralization of positively charged layers because of steric hindrance, decreasing the LC, as observed for LDH-pravastatin material [ 146 ].…”

Complexes of Ibuprofen Thiazolidin-4-One Derivatives with β-Cyclodextrin: Characterization and In Vivo Release Profile and Biological Evaluation

“…The time (s) that the mice spent licking and/or biting the injected paw was recorded. Depending on the time value, the pain can be classified as neurogenic pain (0 to 5 min), interphase pain (5 to 15 min), and inflammatory pain (15 to 30 min) [19,22,23]. For each group, the mean value (±S.E.)…”

Development of Dipeptide N–acetyl–L–cysteine Loaded Nanostructured Carriers Based on Inorganic Layered Hydroxides

“…The intercalated species studied cover a wide range of properties such as anti-inflammatory, antibiotic, antitumor, anticoagulant, antimicrobial, antidepressant, and antioxidant properties [ 44 , 45 ]. We have worked on the development of LDH host matrices for use as carriers of anionic species derived, for instance, from ibuprofen [ 46 ], sulindac [ 47 ], mefenamic acid [ 48 ], coumaric acid [ 49 , 50 ], pravastatin [ 51 ], naproxen [ 43 ], norbixin [ 52 ], and ciprofloxacin [ 53 ]. For some LDH materials, in vivo tests for phases intercalated with chloride ions (Mg 2 Al–Cl and Zn 2 Al–Cl [ 42 ], Mg 4 FeAl–Cl and Zn 4 FeAl–Cl [ 43 ]), or coumarate (Mg 2 Al–Cou and Zn 2 Al–Cou) [ 49 ] were performed to assess their biocompatibility by intramuscular implants, while in vitro assays of intercalated sulindac (Mg 2 Al–Sul and Zn 2 Al–Sul) [ 47 ] and mefenamate (Mg 2 Al–Mef) [ 48 ] materials were also studied.…”