Propolis-loaded solid lipid nanoparticles targeting H. pylori associated with gastro-intestinal diseases

Propolis is a natural substance rich in polyphenolic and flavonoid compounds, known for its potent antimicrobial and anti-inflammatory properties, particularly effective against pathogens such as Helicobacter pylori ( H. pylori ), which are implicated in the pathogenesis of severe gastric diseases. However, its therapeutic application is limited by poor solubility, low physicochemical stability, and poor bioavailability. To address this limitation, Solid Lipid Nanoparticles (SLNs) containing propolis ethanolic extract (PEE) were developed to enhance its stability and improve PEE biological activity. The PEE, obtained via maceration and characterized using High Performance Liquid Chromatography (HPLC) and spectrophotometric assays, was used for the preparation of eleven SLNs’ formulations (PEE-SLN1-11). PEE-SLN10 emerged as optimal formulation, exhibiting favourable physicochemical features: mean particle size of 161.71 nm, polydispersity index (PDI) of 0.14, ζ-potential of -23.13 mV, and an entrapment efficiency % (EE%) of 86%. Transmission electron microscopy (TEM) and differential scanning calorimetry (DSC) confirmed the nanoscale size, a spherical morphology, and a thermal stability. In vitro studies on PEE-SLN10 demonstrated a gradual release profile of chrysin in simulated gastrointestinal fluids. PEE-SLN10 showed good stability under thermal stress, simulated gastrointestinal conditions, long-term storage and a significant enhancement in permeability and intestinal uptake in Parallel Artificial Membrane Permeability Assay (PAMPA) and EpiIntestinal TM in vitro experimental models. Antibacterial assays revealed improved activity against H. pylori and studies performed in Galleria mellonella in vivo model confirmed the development of a biocompatible and safe formulation.