Naproxen/Layered Double Hydroxide Composites for Tissue-Engineering Applications: Physicochemical Characterization and Biological Evaluation

Abstract

Injured bone tissues can be healed with bone grafts, but this procedure may cause intense pain to the patient. A slow and localized delivery of nonsteroidal anti-inflammatory drugs (NSAIDs) could help to reduce the pain without affecting bone regeneration. The objective of the present study was to use [Mg-Al]-layered double hydroxide (LDH) as a matrix for controlled release of sodium naproxen (NAP). This system could be applied in biomaterial formulations (such as bone grafts) to achieve a local delivery of naproxen. [Mg-Al]-LDH successfully incorporated up to 80% (w/w) of naproxen by the structural reconstruction route, with the [Mg-Al]-LDH interlayer space increasing by 0.55 nm, corresponding to the drug molecule size. The evaluation of the naproxen release kinetics showed that 40% of the drug was delivered over 48 h in aqueous medium (pH 7.4 ± 0.1), indicating the potential of [Mg-Al]-LDH/NAP for local release of naproxen at adequate concentrations. Kinetic modeling showed that the naproxen release process was closely related to the Higuchi model, which considers the drug release as a diffusional process based on Fick’s law. The chemical stability of NAP after the release tests was verified by 1H NMR. The [Mg-Al]-LDH/NAP also exhibited low cytotoxicity toward fibroblast cells (L929 cell line), without modifications in their morphology and adhesion capacity. These results describe a suitable approach for preparing efficient systems for local delivery of nonsteroidal anti-inflammatory drugs for biomedical applications.

Layered double hydroxide-based nanomaterials for biomedical applications

“…In order to alleviate the intense pain during bone grafting procedures, Bernardo et al prepared sodium naproxen (NAP, an anti-inflammatory drug)-intercalated MgAl-LDH. 457 The release of NAP was monitored under simulated physiological conditions, and the results showed that free NAP dissolved immediately, while NAP intercalated into LDH was released slowly over 48 h. This could potentially be applied to effectively relieve pain for an extended period of time from a single dose.…”

Layered Double Hydroxides: A Novel Promising 2D Nanomaterial for Bone Diseases Treatment

“…Also, Berber et al [255] intercalated naproxen (NP) and flurbiprofen (FB) into MgAl-LDH via reconstruction and coprecipitation techniques to prepared NP-LDH and FB-LDH nanocomposites and found that the hydrophilic surface area of drug-LDH composites increased the water penetration into the drug components. In the research of Bernardo et al, [250] MgAl-LDH was successfully combined up to 80% w/w of NP by the structural reconstruction route. Pharmacokinetic studies showed a mild NP release, indicating the potentiality of MgAl-LDH for local and sustained convey of naproxen at adequate concentrations.…”

“…Apart from reducing adverse effects of systematic medication, the double‐layer structure of LDHs can protect the loaded NSAIDs from degradation or first‐pass elimination before being transported to orientated sites thus enhancing their pharmacological effects. [ 250 ] NSAIDs encapsulated between the layers of LDHs can also effectively reduce the damage of drugs to gastric mucosa because of the anti‐acid property of LDHs. [ 251 ] During the last decade, LDHs incorporated with different NSAIDs through various technologies such as ion exchange and coprecipitation have been widely researched.…”