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

Cunha, Vanessa R. R.; Guilherme, Viviane A.; Paula, Eneida de; Araújo, Daniele Ribeiro de; Silva, Renan O.; Medeiros, Jand Venes R.; Leite, José Roberto S. A.; Petersen, Philippe Alexandre Divina; Földvári, Marianna; Petrilli, Helena Maria; Constantino, Vera Regina Leopoldo

doi:10.1016/j.msec.2015.08.037

Cited by 47 publications

(25 citation statements)

References 40 publications

(44 reference statements)

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“…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 . The mefenamate confinement in the LDH structure decreased its hemolytic effect and potentiated its anti‐inflammatory and analgesic effects.…”

Section: Introductionmentioning

confidence: 64%

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

Kang

Fernandes

Silva

et al. 2017

Adv Healthcare Materials

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The effect of LDH samples comprised of chloride anions intercalated between positive layers of magnesium/aluminum (Mg-Al LDH) or zinc/aluminum (Zn-Al LDH) chemical composition on pre-osteoblast performance is investigated. Non-cytotoxic concentrations of both LDHs modulated pre-osteoblast adhesion by triggering cytoskeleton rearrangement dependent on recruiting of Cofilin, which is modulated by the inhibition of the Protein Phosphatase 2A (PP2A), culminating in osteoblast differentiation with a significant increase of osteogenic marker genes. The alkaline phosphatase (ALP) and bone sialoprotein (BSP) are significantly up-modulated by both LDHs; however, Mg-Al LDH nanomaterial promoted even more significance than both experimental controls, while the phosphorylations of mitogen-activated protein kinase (MAPKs)- extracellular signal-regulated kinases (ERK) and c-Jun N-terminal kinase (JNK) significantly increased. MAPK signaling is necessary to activate Runt-related transcription factor 2 (RUNX2) gene. Concomitantly, it is also investigated whether challenged osteoblasts are able to modulate osteoclastogenesis by investigating both osteoprotegerin (OPG) and Receptor activator of nuclear factor kappa-ligand (RANKL) in this model; a dynamic reprogramming of both these genes is found, suggesting LDHs in modulating osteoclastogenesis. These results suggest that LDHs interfere in bone remodeling, and they can be considered as nanomaterials in graft-based bone healing or drug-delivery materials for bone disorders.

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Section: Introductionmentioning

confidence: 64%

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

Kang

Fernandes

Silva

et al. 2017

Adv Healthcare Materials

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“…The basal spacing of (003) reflection in blank LDH (Figure 3a) was 8.8 Å calculated by (00l) reflection, which could be attributed to the NO 3 -guests in the interlayer region. 36 When PRN is being intercalated, as shown in Figure 3b, the (003) basal reflection shifted to lower 2θ angle from 10° to 7°, corresponding to an increase of the interlayer distance from 8.8 Å to 12.7 Å. This result indicated that PRN was intercalated into the galleries of LDH.…”

Section: Xrdmentioning

confidence: 88%

Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery

Xu¹,

Xu²,

Gu³

et al. 2018

IJN

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Background To enhance ocular bioavailability, the traditional strategies have focused on prolonging precorneal retention and improving corneal permeability by nano-carriers with positive charge, thiolated polymer, absorption enhancer and so on. Glycylsarcosine (GS) as an active target ligand of the peptide tranpsporter-1 (PepT-1), could specific interact with the PepT-1 on the cornea and guide the nanoparticles to the treating site. Purpose The objective of the study was to explore the active targeting intercalated nanocomposites based on chitosan-glutathione-glycylsarcosine (CG-GS) and layered double hydroxides (LDH) as novel carriers for the treatment of mid-posterior diseases. Materials and methods CG-GS-LDH intercalated nanocomposites were prepared by the coprecipitation hydrothermal method. In vivo precorneal retention study, ex vivo fluorescence images, in vivo experiment for distribution and irritation were studied in rabbits. The cytotoxicity and cellular uptake were studied in human corneal epithelial primary cells (HCEpiC). Results CG-GS-LDH nanocomposites were prepared successfully and characterized by FTIR and XRD. Experiments with rabbits showed longer precorneal retention and higher distribution of fluorescence probe/model drug. In vitro cytological study, CG-GS-LDH nanocomposites exhibited enhanced cellular uptake compared to pure drug solution. Furthermore, the investigation of cellular uptake mechanisms demonstrated that both the active transport by PepT-1 and clathrin-mediated endocytosis were involved in the internalization of CG-GS-LDH intercalated nanocomposites. An ocular irritation study and a cytotoxicity test indicated that these nanocomposites produced no significant irritant effects. Conclusions The active targeting intercalated nanocomposites could have great potential for topical ocular drug delivery due to the capacity for prolonging the retention on the ocular surface, enhancing the drug permeability through the cornea, and efficiently delivering the drug to the targeted site.

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“…It is worth to emphasize that the LDHs in the form of chloride were chosen since they are frequently taken as precursors for the preparation of LDH intercalated with drugs by ion exchange method. When using co-precipitation method for LDH–drug synthesis, metal cations in the form of chloride salts are used as reagents and Cl − can be co-intercalated with drugs, as observed for pravastatin and mefenamate LDH carrier 16 32 .…”

Section: Discussionmentioning

confidence: 99%

“…The biocompatibility of LDH has been explored by in vitro tests such as cell viability tests 12 13 , lactate dehydrogenase leakage assay 12 13 14 15 , inflammatory mediators analysis 12 , hemolysis assay 15 16 17 , thrombosis assay 17 , lipid peroxidation 18 , reactive oxygen species (ROS) generation 12 14 and apoptosis 12 14 . On the other hand, the in vivo biocompatibility and the therapeutic potential of LDH particles have been investigated by a minor number of assays through the analysis of biodistribution and accumulation in tissues 18 19 20 21 , stomach lesions 22 , therapeutic effects as anti-tumor 23 and anti-inflammatory activities 16 . Latterly, interesting reports have explored the usage of LDH as a grout material in bone cement for implant in tibia 24 , and as a coating to middle ear prostheses 25 .…”

mentioning

confidence: 99%

Accessing the biocompatibility of layered double hydroxide by intramuscular implantation: histological and microcirculation evaluation

Cunha

Souza

Martins

et al. 2016

Sci Rep

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Biocompatibility of layered double hydroxides (LDHs), also known as hydrotalcite-like materials or double metal hydroxides, was investigated by in vivo assays via intramuscular tablets implantation in rat abdominal wall. The tablets were composed by chloride ions intercalated into LDH of magnesium/aluminum (Mg2Al-Cl) and zinc/aluminum (Zn2Al-Cl). The antigenicity and tissue integration capacity of LDHs were assessed histologically after 7 and 28 days post-implantation. No fibrous capsule nearby the LDH was noticed for both materials as well any sign of inflammatory reactions. Sidestream Dark Field imaging, used to monitor in real time the microcirculation in tissues, revealed overall integrity of the microcirculatory network neighboring the tablets, with no blood flow obstruction, bleeding and/or increasing of leukocyte endothelial adhesion. After 28 days Mg2Al-Cl promoted multiple collagen invaginations (mostly collagen type-I) among its fragments while Zn2Al-Cl induced predominantly collagen type–III. This work supports previous results in the literature about LDHs compatibility with living matter, endorsing them as functional materials for biomedical applications.

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

Abstract: This work shows the increase of the anti-inflammatory and antinociceptive potential of the drug confined into the LDH, as well as, its hemolytic effect.

Cited by 47 publications

References 40 publications

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

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

Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery

Accessing the biocompatibility of layered double hydroxide by intramuscular implantation: histological and microcirculation evaluation

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