Baicalin-Chlorogenic Acid Self-Assembled Nanoparticles: A Carrier-Free Nano-Formulation for the Treatment of Acute Pharyngitis.

Background/

Objectives

Baicalin (BA), a natural flavonoid with anti-inflammatory activity, shows promise for treating acute pharyngitis (AP) but its clinical application is hindered by poor water solubility and low oral bioavailability. Based on the clinically validated traditional Chinese medicine formula Pudilan Oral Liquid, we identified that BA and chlorogenic acid (CGA) can self-assemble into nanocomplexes (BA-CGA@NPs). This study aims to construct such a nanocomplex to enhance BA absorption and anti-AP efficacy with favorable biocompatibility.

Methods

BA-CGA@NPs were prepared via supramolecular self-assembly and characterized by dynamic light scattering (DLS), X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and molecular dynamics simulation (MDS). In vivo pharmacokinetics evaluated BA absorption. Biocompatibility and therapeutic efficacy were assessed using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and an AP rat model.

Results

BA-CGA@NPs were successfully formed with enhanced biocompatibility. In vitro, they reduced nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) in macrophages. In AP rats, oral BA-CGA@NPs significantly increased systemic BA exposure, ameliorated pharyngeal histopathology, and lowered IL-1β, TNF-α, and interleukin-6 (IL-6) in serum and pharyngeal tissue, outperforming free BA or CGA alone. Mechanistic studies suggested that the anti-inflammatory effect was associated with modulation of the Toll-like receptor 4 (TLR4)/MyD88/Nuclear factor-κB (NF-κB) signaling pathway.

Conclusions

Self-assembled BA-CGA@NPs enhance BA absorption and biocompatibility, alleviating AP inflammation through mechanisms associated with modulation of the TLR4/MyD88/NF-κB pathway, offering a promising nano-traditional Chinese medicine strategy for poorly soluble active ingredients.