Modulation of Inflammatory Mediators by Polymeric Nanoparticles Loaded with Anti-Inflammatory Drugs

Abstract

The first-line treatment of osteoarthritis is based on anti-inflammatory drugs, the most currently used being nonsteroidal anti-inflammatory drugs, selective cyclooxygenase 2 (COX-2) inhibitors and corticoids. Most of them present cytotoxicity and low bioavailability in physiological conditions, making necessary the administration of high drug concentrations causing several side effects. The goal of this work was to encapsulate three hydrophobic anti-inflammatory drugs of different natures (celecoxib, tenoxicam and dexamethasone) into core-shell terpolymer nanoparticles with potential applications in osteoarthritis. Nanoparticles presented hydrodynamic diameters between 110 and 130 nm and almost neutral surface charges (between −1 and −5 mV). Encapsulation efficiencies were highly dependent on the loaded drug and its water solubility, having higher values for celecoxib (39–72%) followed by tenoxicam (20–24%) and dexamethasone (14–26%). Nanoencapsulation reduced celecoxib and dexamethasone cytotoxicity in human articular chondrocytes and murine RAW264.7 macrophages. Moreover, the three loaded systems did not show cytotoxic effects in a wide range of concentrations. Celecoxib and dexamethasone-loaded nanoparticles reduced the release of different inflammatory mediators (NO, TNF-α, IL-1β, IL-6, PGE2 and IL-10) by lipopolysaccharide (LPS)-stimulated RAW264.7. Tenoxicam-loaded nanoparticles reduced NO and PGE2 production, although an overexpression of IL-1β, IL-6 and IL-10 was observed. Finally, all nanoparticles proved to be biocompatible in a subcutaneous injection model in rats. These findings suggest that these loaded nanoparticles could be suitable candidates for the treatment of inflammatory processes associated with osteoarthritis due to their demonstrated in vitro activity as regulators of inflammatory mediator production.

Rhoifolin loaded in PLGA nanoparticles alleviates oxidative stress and inflammation in vitro and in vivo

“…Various studies have reported on polymeric NPs as drug delivery systems for different classes of drugs to enhance their solubility, efficacy and bioavailability. [54][55][56][57][58] In this study, we developed an NP formulation for ROF, a promising bioactive flavonoid, based on PLGA. PLGA-based polymeric NPs have been previously employed to enhance the bioavailability, biological activity, and water solubility of various natural products.…”

Emodin ameliorates acute pancreatitis‑induced lung injury by suppressing NLRP3 inflammasome‑mediated neutrophil recruitment

“…Additionally, DEX has been shown to act as a non-specific immune inhibitor (42). It was reported that its use inhibited the production of numerous inflammatory mediators and increased the synthesis of proteins associated with anti-inflammatory responses (43). Its use for therapeutic intervention has been reported in SAP-associated ALI (44).…”

Nanoarchitectonics of Cartilage-Targeting Hydrogel Microspheres with Reactive Oxygen Species Responsiveness for the Repair of Osteoarthritis

“…However, this technique has some disadvantages, including large operative trauma and economic burden for the individuals affected. The conventional strategy before surgery is the use of corticosteroids such as dexamethasone (Dex), which can alleviate inflammation and reduce the degradation of the chondrocyte extracellular matrix, but corticosteroids can not reverse the progression of OA. , Kartogenin (KGN) can promote the chondrogenic differentiation of stem cells by regulating the CBFβ-RUNX1 pathway and prevent the degeneration of OA-induced cartilage and subchondral bone. , Notably, the low water solubility and fast removal of these drugs result in poor intra-articular delivery efficiency . Consequently, the design and optimization of an intra-articular dual-drug delivery system can provide a meaningful strategy to mitigate the inflammatory response and promote chondrocyte differentiation in OA therapy.…”