Optimized co-delivery of curcumin and methylprednisolone using polyvinyl alcohol-coated CuO nanoparticles for synergistic rheumatoid arthritis treatment

The combination of methylprednisolone (MPDL) and curcumin (CUR) for treating rheumatoid arthritis (RA) offers several therapeutic advantages. This synergy allows for a reduction in the dosage of methylprednisolone, minimizing potential side effects associated with long-term steroid use while maintaining or enhancing the treatment's effectiveness. The objective of this study is to prepare drug carriers for MPDL and CUR aimed at treating RA, utilizing Freund's Complete Adjuvant-induced arthritic rat model (AIA). CuO nanoparticles (NPs) were synthesized using ultrasound by reducing copper (II) sulfte pentahydrate with sodium borohydride in a basic solution. Subsequently, these nanoparticles were incrementally added to a polyvinyl alcohol (PVA) solution to ensure controlled integration of PVA-coated CuO NPs. Field Emission Scanning Electron Microscopy (FE-SEM) analysis revealed that the CuO nanoparticles and PVA-coated CuO NPs averaged sizes of 50.7 nm and 104.8 nm, respectively. Furthermore, the PVA-coated CuO NPs demonstrated remarkable biocompatibility, with cell viability ranging from 88.1 % to 92.1 % at concentrations of 0.1 μg/mL and 50 μg/mL after 72 h, as validated through the MTT assay. The PVA-coated CuO NPs exhibited a more controlled and gradual drug release profile for both CUR and MPDL when compared to the PVA matrix. CUR@MPDL@PVA-coated CuO NPs demonstrated the most substantial reduction in hind paw swelling and the minimal clinical scores among all treatment groups, signaling enhanced anti-inflammatory effects. CUR@MPDL@PVA-coated CuO NPs also notably reduced the concentrations of pro-inflammatory cytokines TNF-α and IL-1β when measured against the AIA rats and the groups treated with free agents. Therefore, CUR@MPDL@PVA-coated CuO nanoparticles can be used in biomedical applications due to their size, biocompatibility, and anti-inflammatory properties.