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

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, 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.