In vitro–in vivo assessments of apocynin-hybrid nanoparticle-based gel as an effective nanophytomedicine for treatment of rheumatoid arthritis

Apocynin (APO), a well-known bioactive plant-based phenolic phytochemical with renowned anti-inflammatory and antioxidant pharmacological activities, has recently emerged as a specific nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) oxidase inhibitor. As far as we know, no information has been issued yet regarding its topical application as a nanostructured-based delivery system. Herein, APO-loaded Compritol(®) 888 ATO (lipid)/chitosan (polymer) hybrid nanoparticles (APO-loaded CPT/CS hybrid NPs) were successfully developed, characterized, and optimized, adopting a fully randomized design (3(2)) with two independent active parameters (IAPs), namely, CPT amount (X(A)) and Pluronic(®) F-68 (PF-68) concentration (X(B)), at three levels. Further in vitro–ex vivo investigation of the optimized formulation was performed before its incorporation into a gel base matrix to prolong its residence time with consequent therapeutic efficacy enhancement. Subsequently, scrupulous ex vivo–in vivo evaluations of APO-hybrid NPs-based gel (containing the optimized formulation) to scout out its momentous activity as a topical nanostructured system for beneficial remedy of rheumatoid arthritis (RA) were performed. Imperatively, the results support an anticipated effectual therapeutic activity of the APO-hybrid NPs-based gel formulation against Complete Freund’s Adjuvant-induced rheumatoid arthritis (CFA-induced RA) in rats. In conclusion, APO-hybrid NPs-based gel could be considered a promising topical nanostructured system to break new ground for phytopharmaceutical medical involvement in inflammatory-dependent ailments. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13346-023-01360-5.