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Effects of lipid membrane composition on the distribution of biocidal guanidine oligomer with solid supported lipid

Yeonjeong Ha1, Jung-Hwan Kwon1

  • 1Division of Environmental Science and Ecological Engineering, Korea University 145 Anam-ro Seongbuk-gu Seoul 02841 Republic of Korea junghwankwon@korea.ac.kr +82 2 3290 3041.

RSC Advances
|May 6, 2022
PubMed

Insights

Polyhexamethylene guanidine (PHMG) distribution into lipid membranes is crucial for understanding its respiratory toxicity. PHMG preferentially accumulates in anionic lipid membranes, influencing its deposition in the lungs.

Area of Science:

  • Biochemistry
  • Toxicology
  • Materials Science

Background:

  • Polyhexamethylene guanidine (PHMG) is a widely used antimicrobial agent.
  • Inhalation exposure to PHMG has led to severe lung damage, including fibrosis.
  • Understanding PHMG's interaction with cell membranes is key to assessing respiratory risks.

Purpose of the Study:

  • To quantify the distribution of PHMG between lipid membranes and water.
  • To investigate how different lipid membrane compositions affect PHMG distribution.
  • To elucidate the relationship between membrane properties and PHMG deposition in respiratory systems.

Main Methods:

  • Development of a quantitative method to determine the distribution constant (K_lipw) of PHMG.
  • Utilizing solid-supported lipid membranes with varying compositions (anionic, cationic, zwitterionic lipids, cholesterol).
  • Evaluating the effects of lipid head groups, acyl chain saturation, and cholesterol content on K_lipw.

Main Results:

  • PHMG rapidly accumulated in anionic lipid membranes compared to cationic or zwitterionic membranes.
  • K_lipw values were higher in anionic/zwitterionic lipid mixtures than in anionic lipids alone.
  • Increased single acyl chain lipid content and decreased cholesterol content enhanced PHMG distribution into membranes.

Conclusions:

  • PHMG exhibits preferential adsorption to anionic lipid head groups.
  • Lipid membrane composition, including charge, phase separation, spontaneous curvature, and packing density, significantly influences PHMG distribution.
  • These findings provide insights into the depositional flux and toxic mechanisms of PHMG in the respiratory tract.

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