Poly ε-Caprolactone Nanoparticles for Sustained Intra-Articular Immune Modulation in Adjuvant-Induced Arthritis Rodent Model

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder with synovitis and articular pathology as its primary expositions. Leflunomide (Lfd) is an anti-rheumatic drug that is effective in the treatment of RA, but displays severe side effects upon prolonged systemic administration. Local therapy might represent a promising strategy to treat rheumatoid arthritis without eliciting systemic adverse effects. In this study, leflunomide-loaded poly(ε-caprolactone) nanoparticles (Lfd-NPs) were prepared and assessed as a local drug delivery system capable of alleviating RA-associated inflammation. Lfd-NPs were optimized using the Quality by Design (QbD) approach, applying a 32 full factorial design. In vitro drug release from NPs was examined in simulated synovial fluid. In addition, the in vivo efficacy of Lfd-NPs was evaluated in the Adjuvant Induced Arthritis (AIA) rodent model. Sustained drug release in simulated synovial fluid was observed for up to 168 h. A gradual reduction in paw volume and knee diameter was observed over the course of treatment, indicating the regression of the disease. In addition, significant reductions in serum proinflammatory markers and cytokines, including the C-reactive protein (CRP), rheumatoid factor (RF), TNF-α, IL1-β, and IL-6, were verified upon treatment with Lfd-NPs, suggesting the modulation of immune responses at the pathological site. Most importantly, no remarkable signs of toxicity were observed in Lfd-NP-treated animals. Collectively, intra-articularly administered Lfd-NPs might represent a potential therapeutic alternative to systemically administered drugs for the treatment of rheumatoid arthritis, without eliciting systemic adverse effects.

In Vitro Cytotoxicity and In Vivo Antitumor Activity of Lipid Nanocapsules Loaded with Novel Pyridine Derivatives

“…This size range of all formulated LPNCs is large enough (>50 nm) to evade hepatic sequestration [ 38 ], while it is small enough to escape phagocytosis (<250 nm) [ 39 ]. Of note, the polydispersity index (PDI) of all formulations is <0.3, indicating narrow size distribution [ 40 ].…”

Formulation of silymarin surface modified vesicles: In vitro characterization to cell viability assessment

“…The spectroscopy study was performed to check the drug polymer interaction study ( Singh et al, 2022 ). Each sample (free SLR, lipid, cholesterol, chitosan and SLR lipid vesicles (F3, F3C1).…”

Phytosomes as a Plausible Nano-Delivery System for Enhanced Oral Bioavailability and Improved Hepatoprotective Activity of Silymarin

“…Drug content (%) was calculated using the following formula: The chemical interaction between phytosomal components was studied using an infrared (IR) spectra matching approach using a FTIR spectrometer (Alpha Bruker, Berlin, Germany). The IR spectrum of the pure silymarin, soybean phosphatidyl choline (SPC), physical mixture of silymarin and SPC (1:1), and optimized silymarin phytosomal formulation was obtained by scanning within the wavelength range of 4000 to 500 cm −1 [39].…”