Proof of pore formation and biophysical perturbations through a 2D amoxicillin-lipid membrane interaction approach

Area of Science:

• Biophysics
• Biochemistry
• Materials Science

Background:

• Amoxicillin is a key antibiotic for treating *Helicobacter pylori* infections.
• Current treatments face limitations due to side effects and poor patient compliance.
• Amoxicillin toxicity is linked to lower pH environments.

Purpose of the Study:

• To investigate the influence of pH on amoxicillin's toxicity.
• To understand amoxicillin's interaction with biological membranes at varying pH levels.

Main Methods:

• Utilized 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid monolayers.
• Employed isotherm measurements, infrared reflection-absorption spectroscopy, grazing incident X-ray diffraction, and Brewster angle microscopy.
• Examined DPPC monolayers across pH 1.2, 5, and 7.4, with and without amoxicillin.

Main Results:

• DPPC monolayers exhibited distinct structural and packing properties at different pH values.
• Amoxicillin's interaction with DPPC monolayers was pH-dependent.
• Acidic pH (1.2 and 5) induced significant perturbations, including pore formation, visualized by Brewster angle microscopy.
• At pH 7.4, amoxicillin showed effects at lower pressures, with partial restoration of monolayer properties at 30 mN/m.

Conclusions:

• The study demonstrates that pH significantly influences amoxicillin's interaction with and perturbation of lipid membranes.
• Observed perturbations, particularly pore formation at acidic pH, may correlate with amoxicillin's known toxicity.
• Findings provide insights into amoxicillin's side effects and potential strategies for safer therapeutic use.