Investigating the Effects of Charge and Molecular Weight of Pharmaceutical Polymers on Their Biomolecular Interaction with Bilayer Membrane

Abstract

Background: The interaction between polymers and biological membranes is crucial for the development of effective drug delivery systems. Objectives: Our study aims to address this knowledge gap by investigating the interactions between a range of biological and synthetic polymers [cellulose, chitosan, polyethyleneimine (PEI), alginate, and polylactic-co-glycolic acid (PLGA)] and a lipid bilayer membrane. Methods: In this study, molecular dynamics (MD) simulations were used to investigate the interactions between various polymers and a lipid bilayer membrane. Results: The results show that the polymers interact with the lipid bilayer through a combination of electrostatic and hydrogen bonding forces, with PEI exhibiting the most significant effect on membrane disruption. The study also highlights the importance of understanding the binding free energy between polymers and lipids, with PEI having the highest binding energy. The order parameter analysis reveals that PEI significantly influences the order of all lipids, while cellulose and alginate cause lower order and higher flexibility in the acyl chain of the lipids. The lateral diffusion analysis shows that PEI has a significant effect on the lateral diffusion of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and 1-stearoyl-2-oleoylphosphatidylcholine (SOPC) lipids, indicating a higher lateral diffusion coefficient. Conclusions: Overall, this study provides valuable insights into the mechanisms of membrane disruption by polymers and has implications for the design of effective and safe drug delivery systems.