Enhanced Anti‐inflammatory Effects of Diclofenac Delivered Orally via Polyvinylpyrrolidone K30/Silk Fibroin Nanoparticles in a Murine Model of Carrageenan‐Induced Paw Edema

Abstract Diclofenac has a relatively low oral bioavailability (50–60 %) and is quickly metabolized with a half‐life of less than 1 h. Therefore, the oral therapeutic effect of diclofenac is not optimal. This research developed polyvinylpyrrolidone K30‐functionalized silk fibroin nanoparticles as an effective delivery system for diclofenac (FNPs‐PVP‐DC). The FNPs‐DC and FNPs‐PVP‐DC were formulated by two methods of adsorption and solvent exchange. Depending on the formulation factors, the obtained particles exhibited different properties of nano‐scale sizes (400–800 nm), narrow size distribution, negatively charged surfaces (−17 to −19 mV), high PVP K30 incorporation (23 %–50 %), pHpzc of ~6.6, and appropriate chemical interactions. Interestingly, particles formulated by the adsorption method showed low drug encapsulation efficiencies of <15 %, whereas the solvent exchange method yielded moderate results of ~40 %. The FNPs‐DC possessed aggregated patterns, while the FNPs‐PVP‐DC were more uniformly distributed. All formulations limited diclofenac release (<20 %) under gastric conditions and sustained its release in the intestinal environment. In in‐vivo carrageenan‐induced paw edema mice model, the FNPs‐PVP‐DC demonstrated a 20–30 % higher anti‐inflammatory effect and a faster onset of action (within 1 h) compared to pure diclofenac at the same dose (5 mg/kg). These findings suggest that FNPs‐PVP‐DC have promising potential as novel oral anti‐inflammatory products.