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Naringin (NAR), a naturally occurring essential flavonoid, present in grapefruit and Chinese herbal medicines, creates great interest in researchers due to its diverse biological and pharmacological activities. However, further development of NAR is hindered due to its poor water solubility and dissolution rates in GIT. To address these limitations, in this study, we report polymeric nanoparticles (NPs) of NAR (NAR-PLGA-NPs) for enhancing the oral NAR efficiency, with a biodegradable polymer (PLGA) to improve its absorption and bioavailability. NAR-PLGA-NPs were fabricated by a modified solvent emulsification-evaporation technique. Physicochemical properties were evaluated by SEM, particle size distribution, entrapment efficiency, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). In vitro drug release and ex vivo permeation studies were carried out in phosphate buffer (pH 6.8) for 24 h . Furthermore, in vivo anti-arthritic studies were performed on a mouse model, and the results were compared with free NAR. The modulation of inflammatory mediators was also evidently supported by docking studies. Optimized nanoformulation FN4 (NAR-PLGA-NPs) prepared with acetone-ethanol (2:1) as a solvent system in a combination of stabilizers, i.e., poloxamer-188 and sodium deoxylate (1:1), along with 2% PVA solution, was prepared. From size characterization studies, it was observed that nanoformulations possessed a low particle size (179.7 ± 2.05 nm), a low polydispersity index (0.206 ± 0.001), and a negative zeta potential (-9.18 ± 0.78 mV) with a maximum entrapment efficiency (74 ± 3.61%). The drug release followed a Korsmeyer-Peppas release kinetic model (anomalous non-Fickian diffusion), providing greater NAR release after lyophilization (82.11 ± 3.65%) drug release in pH 6.8 phosphate buffer for 24 h. Ex vivo permeation analysis through an isolated goat intestinal membrane revealed 80.02 ± 3.69% drug release in 24 h. Encapsulation of a drug into PLGA is well described by the results of FTIR, DSC, and XRD. Finally, the therapeutic efficacy of optimized FN4 (NAR-PLGA-NPs) and its possible application on RA were further confirmed in a Freund's complete adjuvant-induced rat arthritic model as against free NAR at a dose of 20 mg/kg body wt. Our findings demonstrate that sustained action of NAR from optimized FN4 NPs with a rate-controlling polymeric carrier system exhibited prolonged circulation time and reduced arthritic inflammation, hence indicating the possibility as a novel strategy to secure the unpropitious biological interactions of hydrophobic NAR in a gastric environment.

Naringin as Sustained Delivery Nanoparticles Ameliorates the Anti-inflammatory Activity in a Freund’s Complete Adjuvant-Induced Arthritis Model