Enhanced oral bioavailability and antiviral efficacy of phillygenin via a self-nanoemulsifying drug delivery system in IBV-infected broilers

Infectious bronchitis (IB) poses a significant global economic threat to the poultry industry. Phillygenin (PHI), a lignan compound possessing antiviral activity, has its clinical application limited by poor aqueous solubility and low oral bioavailability. To overcome these limitations, a self-nanoemulsifying drug delivery system loaded with PHI (PHI SNEDDS) was prepared. The resulting formulation exhibited uniform spherical nanoparticles with a size of 35.06 ± 0.64 nm, a zeta potential of -2.22 ± 0.27 mV, and a polydispersity index (PDI) of 0.180 ± 0.006, indicating high physical stability. In vitro release studies showed that PHI SNEDDS significantly enhanced both the rate and extent of drug release. A pharmacokinetic study in broilers revealed that the relative oral bioavailability of PHI SNEDDS reached 388.34% compared to the PHI suspension, accompanied by significantly increased maximum plasma concentration (C max ) and area under the curve (AUC 0-t ) ( P < 0.001), which confirms a substantial enhancement in absorption. In an IBV-infected broiler model, the SNEDDS formulation potentiated the antiviral efficacy of PHI. Compared to the IBV group and the PHI suspension group, PHI SNEDDS markedly enhanced antiviral efficacy, alleviating weight loss, clinical signs, and pathological damage in the trachea, lungs, and kidneys. It also significantly reduced viral load, virus shedding, and IBV-N protein expression ( P < 0.05), while increasing anti-IBV antibody levels ( P < 0.05), collectively indicating effective suppression of viral replication and enhancement of the host immune response. In conclusion, PHI SNEDDS effectively improved the solubility, bioavailability, and in vivo anti-IBV activity of PHI, demonstrating considerable potential as a therapeutic strategy for IB and offering a robust solution for administering hydrophobic active compounds.