Introduction: To overcome the poor oral bioavailability of Panax Notoginseng Saponins (PNS) caused by low permeability and acid instability, this study designed bioadhesive microspheres co-loaded with PNS and N-acetyl-L-cysteine (PNS-NAC-BMS). This system aims to protect PNS from gastric degradation and enhance its intestinal permeability and oral bioavailability. Methods: PNS-NAC-BMS were fabricated via solvent evaporation and characterized for morphology, particle size, drug loading, encapsulation efficiency, mucoadhesion, and in vitro release. Permeability was assessed using Purified Mucin Intestinal Mucus (PIM), Artificial Intestinal Mucus (AIM), and Rat Native Intestinal Mucus (RIM). Oral bioavailability was assessed through rat pharmacokinetic studies. Results: PNS-NAC-BMS exhibited spherical morphology with uniform particle sizes. They achieved high encapsulation efficiency (91.55%) and intestinal adhesion (94.83%), with sustained release. The system showed high apparent permeability coefficients across three models (PIM, AIM, RIM). Pharmacokinetic studies revealed prolonged release and a 2.6-fold increase in oral bioavailability versus PNS Active Pharmaceutical Ingredients (PNS APIs). Discussion: Recently, patents (US 20230338448, CN 118873498) describe PNS delivery using nanocomposites and liposomes. However, none exist for NAC-modified adhesive microspheres, underscoring the novelty of this study. The BMS system significantly improves the oral bioavailability through combined mucoadhesion and NAC-mediated penetration. NAC promotes drug transport across the mucus barrier by cleaving mucin disulfide bonds and increasing lipid solubility. However, promising long-term stability, scalable production, and mucosal safety of NAC require further study. Conclusion: PNS-NAC-BMS significantly enhanced intestinal adhesion and sustained drug release, thereby synergistically improving intestinal mucus permeability and oral bioavailability, demonstrating potential as an effective oral drug delivery system.
Qiu et al. (Tue,) studied this question.