A novel mucoadhesive nanofabrication strategy for levofloxacin hemihydrate optimized via central composite design for Helicobacter pylori therapy

Background: Helicobacter pylori (H. pylori), a gram-negative bacterium that causes gastritis, peptic ulcers, and gastric cancer, infects more than half of the global population. The recommended levofloxacin-based nanotherapy can be deployed to overcome rapid gastric emptying of the drug, inadequate drug concentration at the site of action, and the protective mucosal layer. The research established a goal to design and enhance Levofloxacin Hemihydrate(LH) Mucoadhesive Nanoparticles (LMNP) for better drug retention on stomach mucosa and mucosal adhesion, site-specific prolonged drug delivery against H. pylori. Methodology: The LMNP nanoparticles were prepared through ionic gelation of chitosan (CT), carbopol 974P(CP), and N-Acetylcysteine (NAC) before optimizing them using Central Composite Design (CCD) within Response Surface Methodology. The study used FTIR, DSC, XRD, SEM, particle size, zeta potential, entrapment efficiency (EE%), in vitro cumulative drug release %, and mucoadhesive strength (MS%) tests for characterization. Results and Discussion: The optimized LMNP formulation had a particle size of 245.4 ± 1.254 nm, an EE% of 72 ± 2.246%, and Prolonged drug release over 6 hours with in vitro CDR of 99.98 ± 0.115%, which fits the gastric mucus turnover time. FTIR, DSC, and XRD confirmed the compatibility of drug excipients. SEM revealed uniform spherical particles, and MS% was 62 ± 2.315%. The size of the particles and their entrapment efficiency , mucoadhesive properties, and in vitro cumulative drug release were influenced by CT and CP, but NAC enhanced mucopenetration effects. The CCD model successfully established formulation behavior and confirmed synergistic interactions among the excipients. By enhancing matrix formation and swelling, the combined impact of CT and CP significantly influenced. Conclusion: The LMNP system developed by employing CCD designs and ionic gelation methodology demonstrated promising characteristics for gastric retention and prolonged drug release , which could enhance H. pylori clearance rates. The drug delivery platform presents a practical, biocompatible solution to address challenges in conventional therapy.