Advanced interpenetrating polymer networks for innovative gastroretentive formulations targeting Helicobacter pylori gastric colonization

Eur J Pharm Sci. 2024 Sep 1:200:106840. doi: 10.1016/j.ejps.2024.106840. Epub 2024 Jun 21.

Abstract

The escalating challenges of Helicobacter pylori-induced gastric complications, driven by rising antibiotic resistance and persistent cancer risks, underscore the demand for innovative therapeutic strategies. This study addresses this urgency through the development of tailored semi-interpenetrating polymer networks (semi-IPN) serving as gastroretentive matrices for amoxicillin (AMOX). They are biodegradable, absorb significant volume of simulated gastric fluid (swelling index > 360 %) and exhibit superporous microstructures, remarkable mucoadhesion, and buoyancy. The investigation includes assessment at pH 1.2 for comparative analysis with prior studies and, notably, at pH 5.0, reflecting the acidic environment in H. pylori-infected stomachs. The semi-IPN demonstrated gel-like structures, maintaining integrity throughout the 24-hour controlled release study, and disintegrating upon completing their intended function. Evaluated in gastroretentive drug delivery system performance, AMOX release at pH 1.2 and pH 5.0 over 24 h (10 %-100 %) employed experimental design methodology, elucidating dominant release mechanisms. Their mucoadhesive, buoyant, three-dimensional scaffold stability, and gastric biodegradability make them ideal for accommodating substantial AMOX quantities. Furthermore, exploring the inclusion of the potassium-competitive acid blocker (P-CAB) vonoprazan (VONO) in AMOX-loaded formulations shows promise for precise and effective drug delivery. This innovative approach has the potential to combat H. pylori infections, thereby preventing the gastric cancer induced by this pathogen.

Keywords: Amoxicillin; Gastric cancer; Guar gum; Helicobacter pylori; Korsmeyer-Peppas model; Mucoadhesive polymers; Semi-IPN; Superporous matrix; Vonoprazan.

MeSH terms

  • Amoxicillin* / administration & dosage
  • Amoxicillin* / chemistry
  • Amoxicillin* / pharmacology
  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Delayed-Action Preparations / administration & dosage
  • Drug Delivery Systems / methods
  • Drug Liberation
  • Gastric Mucosa* / drug effects
  • Gastric Mucosa* / metabolism
  • Gastric Mucosa* / microbiology
  • Helicobacter Infections / drug therapy
  • Helicobacter Infections / microbiology
  • Helicobacter pylori* / drug effects
  • Humans
  • Hydrogen-Ion Concentration
  • Polymers* / administration & dosage
  • Polymers* / chemistry
  • Pyrroles / administration & dosage
  • Pyrroles / chemistry
  • Pyrroles / pharmacology
  • Sulfonamides

Substances

  • Amoxicillin
  • Anti-Bacterial Agents
  • Polymers
  • Delayed-Action Preparations
  • Pyrroles
  • 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine
  • Sulfonamides