Mucoadhesive lignin-liposome nanocarriers of coptisine: A multifunctional strategy against antibiotic-resistant Helicobacter pylori biofilms

Bioorg Chem. 2026 Mar:170:109399. doi: 10.1016/j.bioorg.2025.109399. Epub 2025 Dec 26.

Abstract

Background: Helicobacter pylori remain a major global health challenge due to rising antibiotic resistance, persistent biofilm formation, and oxidative stress-mediated gastric pathogenesis. Innovative therapeutic approaches are urgently required to overcome the limitations of conventional antibiotic regimens.

Methods: We engineered a novel mucoadhesive nanocarrier (COP-LIG@LIPSNCs) by synergistically integrating biofilm-disrupting lignin nanoparticles with biocompatible liposomal vesicles to encapsulate the bioactive isoquinoline alkaloid coptisine. The formulations were comprehensively characterized using DLS, FTIR, XRD, and TEM. Antibacterial and antibiofilm were evaluated through MIC/MBC assays, time-kill kinetics, confocal bioimaging, and electron microscopy. Cytocompatibility was assessed using L929 fibroblasts, while in vivo mucoadhesion and therapeutic efficacy were investigated in a murine model.

Results: COP-LIG@LIPSNCs exhibited a stable nanoscale size (∼197 nm; PDI 0.152; ζ-potential -31.4 mV, EE% 89.2 ± 1.4 % and LE% 2.1 ± 0.08 %). COP-LIG@LIPSNCs displayed sustained behaviour, releasing 42.28 ± 4.2 % in SGF and 58.17 ± 4.1 % in SIF after 48 h, with strong mucoadhesion. Antibacterial studies demonstrated potent activity against H. pylori (MIC 32 μg/mL; MBC 64 μg/mL), achieving >92 % eradication of planktonic cells and ∼ 89 % disruption of established biofilms within 24 h. CLSM and SEM confirmed nanocarrier penetration, membrane disruption, and biofilm dispersion. Surprisingly, the H. pylori burden of the COP@LIG@LIP group was significantly lower at 1.38 × 104 CFU/g compared to negative control, indicating the effective treatment effect of killing H. pylori in vivo.

Conclusion: COP-LIG@LIPSNCs represent a novel and multifunctional nanoplatform that synergistically combines antimicrobial, antibiofilm, and antioxidant actions. This study pioneers a sustainable strategy using lignin to create an advanced therapeutic alternative, showing significant promise for managing drug-resistant H. pylori infections.

Keywords: Antibiotic resistance; Biofilm; Coptisine; Helicobacter pylori; Lignin nanoparticles; Liposomes; Mucoadhesion.

MeSH terms

  • Animals
  • Anti-Bacterial Agents* / chemical synthesis
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Berberine* / analogs & derivatives
  • Berberine* / chemistry
  • Berberine* / pharmacology
  • Biofilms* / drug effects
  • Dose-Response Relationship, Drug
  • Drug Carriers* / chemistry
  • Drug Resistance, Bacterial / drug effects
  • Helicobacter pylori* / drug effects
  • Helicobacter pylori* / physiology
  • Humans
  • Lignin* / chemistry
  • Lignin* / pharmacology
  • Liposomes / chemistry
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Nanoparticles* / chemistry
  • Particle Size
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Liposomes
  • Berberine
  • Lignin
  • coptisine
  • Drug Carriers