Rutin-loaded chitosan nanoparticles alleviated Freund's adjuvant induced rheumatoid arthritis via modulating oxidative stress and inflammatory parameters in Wistar rats.

Rheumatoid arthritis (RA) is the most common chronic inflammatory disease, primarily affecting the joints and with stromal tissue dysregulation causing chronic inflammation and joint destruction. Rutin is a natural flavonoid with potential therapeutic properties in chronic destructive conditions including rheumatoid diseases. In this study, the protective effects of rutin nanoformulation in an animal model of rheumatoid arthritis caused by Freund's complete adjuvant (FCA) were investigated. Sixty male rats were randomly divided into ten groups including normal, negative control, prednisolone 10 mg/kg (positive control), 3 doses of rutin (15, 30, 45mg/kg), rutin nanoparticles (15, 30, 45 mg/kg), and nanoparticle without rutin, for 28 days. Different behavioral parameters including the open field test, acetone drop test, hot plate test, Von Frey test, and inclined plane test were evaluated. Serum levels of glutathione (GSH), catalase, and nitric oxide as well as histopathological analyses were measured in different groups. Also, matrix metalloproteinase (MMP)-2 and MMP-9 activity were appraised by gelatin zymography. The injection of FCA prolonged the rats' immobility duration in comparison to the control group. Rheumatoid arthritis induction also increased nitric oxide and decreased GSH and catalase levels, while these effects were reversed in the groups that received nanoparticles containing rutin and prednisolone. Rutin nanoparticles suppressed MMP-9 and activated MMP-2. Also, this rutin drug delivery system plays a significant role in the improvement of histopathological symptoms. Considering the improvement of behavioral and tissue symptoms and the modulation of the level of inflammatory cytokines, nanoparticles containing rutin can be proposed as a suitable approach in the management of patients with rheumatoid arthritis.

Electrospun sandwich-structured of polycaprolactone/gelatin-based nanofibers with controlled release of ceftazidime for wound dressing.

In the present work, sandwich-like polycaprolactone/gelatin/polycaprolactone electrospun multilayered mats were implemented to control the release of ceftazidime (CTZ). The outer layers were made from polycaprolactone nanofibers (NFs), and CTZ-loaded gelatin provided an internal layer. The release profile of CTZ from mats was compared with monolayer gelatin mats and chemically cross-linked GEL mats. All the constructs were characterized using scanning electron microscopy (SEM), mechanical properties, viscosity, electrical conductivity, X-ray diffraction (XRD), and Fourier transform-infrared spectroscopy (FT-IR). In vitro cytotoxicity against normal fibroblasts as well as antibacterial activity of CTZ-loaded sandwich-like NFs were investigated by the MTT assay. The results showed that the drug release rate from the polycaprolactone/gelatin/polycaprolactone mat was slower than that of gelatin monolayer NFs, and the rate of release can be adjusted by changing the thickness of hydrophobic layers. The NFs exhibited high activity against Pseudomonas aeruginosa and Staphylococcus aureus, while no significant cytotoxicity was observed against human normal cells. Altogether, the final mat as a predominant antibacterial scaffold can be used for controlled drug release of antibacterial drugs as the wound healing dressings in tissue engineering.

Controlled release of 5-fluorouracil to melanoma cells using a hydrogel/micelle composites based on deoxycholic acid and carboxymethyl chitosan.

5-Fluorouracil (5-FU) is an antimetabolite drug widely used for the treatment of skin cancer. Despite its proven efficacy in treating malignancies, its systemic administration is limited due to severe side effects. To address this issue, topical delivery of 5-FU has been proposed as an alternative approach for the treatment of skin cancer, however, the poor permeability of 5-FU through the skin is still a challenge. Here, we introduced a pH-responsive micellar hydrogel system based on deoxycholic acid micelle (DCA Mic) and carboxymethyl chitosan hydrogel (CMC Hyd) to enhance 5-FU efficacy against skin cancer and reduce its systemic side effects by improving its delivery into the skin. The properties of the Mic/Hyd system were determined by Fourier-transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), zeta sizer, atomic force microscopy (AFM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Drug release studies showed pH-dependent properties of the Hyd. The final formulation was demonstrated to have enhanced anticancer activity than 5-FU against the growth of melanoma cells. The 5-FU@Mic-Hyd could be a promising delivery platform with enhanced efficacy in the management of skin cancer without systemic toxicity.