Enhanced Anti-inflammatory Effect of Puerarin through Optimized Release and Bioavailability via PDLG-Loaded...

Puerarin (PU), a bioactive constituent reported to possess therapeutic effectiveness, but it suffers a drawback of poor bioavailability. In the present study, the PU nanoparticles (PU-NPs) were prepared using solvent-diffusion-evaporation method and optimized using Box-Behnken design (BBD), a response surface methodology for obtaining the optimal material ratio of PU-NPs. Further, PU and PU-NPs were evaluated to assess their cytotoxic effect and in vitro efficiency of inflammatory responses using lipopolysaccharide-sensitive macrophage cell line (RAW264.7). Also, PU-NPs were assessed for, in vivo anti-inflammatory activity using a carrageenan-induced rat paw edema model and an oral pharmacokinetic release study. PU-NPs formulation exhibited smaller particle sizes, an increase in the amorphous structure stability, and a higher dissolution rate, as compared to PU. The relative bioavailability of PU-NPs increased up to five-fold compared to PU suspension, as demonstrated by the parameters like the area under the curve (AUC), t_1/2, and the mean residence time (MRT). It mitigates enhanced cell viability and lowers the production of pro-inflammatory mediators [nitric oxide (NO), tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6)]. Moreover, PU-NPs showed a marked reduction in the development of paw edema at low doses compared to PU in an in vivo carrageenan-induced rat paw edema model. The results of the study affirm the potential of PU-NPs compared to PU in enhancing in vitro and in vivo anti-inflammatory responses by prolonging release and enhancing relative bioavailability.