Computationally-guided multifunctional nanoplatform for enhanced oral delivery and targeted therapy of Helicobacter...

Herbal bioactive ingredients offer considerable promise for the eradication of Helicobacter pylori (H. pylori) due to their inherent non-toxicity, cost-effectiveness, and diverse pharmacological activities. However, their clinical utility is frequently limited by poor oral bioavailability and insufficient accumulation at target sites. In this study, we fabricated a multifunctional nanoplatform for H. pylori-targeted therapy developed through a computationally guided design strategy. Advanced computational methods-including density functional theory (DFT) calculations and molecular dynamics (MD) simulations-were employed to identify tanshinone I (Tan_I) as an optimal herbal candidate for encapsulation within a thiolated fucoidan-polydopamine (PDA-FuSH) nanocarrier. The resulting nanoplatform (T@PDA-FuSH) demonstrated exceptional stability, high drug-loading efficiency, and distinct gastric mucoadhesive properties, attributable to its strong binding affinity for gastric mucin MUC5AC. Furthermore, T@PDA-FuSH exhibited robust bactericidal activity against both standard H. pylori strains and drug-resistant clinical isolates. In vivo evaluation using a H. pylori infected murine model revealed that T@PDA-FuSH effectively reduced H. pylori burden, alleviated inflammatory responses, and promoted the restoration of gastric mucosal integrity. Importantly, this treatment modality preserved the homeostasis of the gastric microbiota, notably enhancing the abundance of beneficial probiotics such as Lactobacillus and Bifidobacterium. Overall, our computationally guided approach provides a novel and promising platform for optimizing the oral delivery of herbal bioactives, significantly enhancing their therapeutic efficacy against H. pylori infection.