Behavior of P85 and P188 Poloxamer Molecules: Computer Simulations Using United-Atom Force-Field

Abstract

To study the interaction between poloxamer molecules and lipid bilayers using molecular dynamics simulation technique with the united-atom resolution, we augmented the GROMOS force-field to include poloxamers. We validated the force-field by calculating the radii of gyration of two poloxamers, P85 and P188, solvated in water and by considering the poloxamer density distributions at the air/water interface. The emphasis of our simulations was on the study of the interaction between poloxamers and lipid bilayer. At the water/lipid bilayer interface, we observed that both poloxamers studied, P85 and P188, behaved like surfactants: the hydrophilic blocks of poloxamers became adsorbed at the polar interface, while their hydrophobic block penetrated the interface into the aliphatic tail region of the lipid bilayer. We also observed that when P85 and P188 poloxamers interacted with damaged membranes that contained pores, the hydrophobic blocks of copolymers penetrated into the membrane in the vicinity of the pore and compressed the membrane. Due to this compression, water molecules were evacuated from the pore.

Surface Plasmon Resonance Study of the Binding of PEO–PPO–PEO Triblock Copolymer and PEO Homopolymer to Supported Lipid Bilayers

“…In other words, the P188 and PEO both interact with the lipid bilayer via initial PEO contact, which would explain the comparable binding. The interaction of the PEO blocks in Poloxamers has been reported in several molecular dynamics simulations 28,65 . After initial contact, the PEO blocks likely remain in close proximity to the lipid head groups positioning the overall P188 molecule for subsequent insertion of the hydrophobic PPO block into the lipid tail region 66 , as suggested by previous studies using Poloxamers with long PPO chains 67 .…”

“…Similarly, in surface plasmon resonance measurements with spherical vesicles adsorbed to a gold surface, 2.5 kDa PEO-C 11 did not appreciably bind, whereas PEO-C 12 bound slightly and PEO-C 14 bound substantially. Molecular dynamics simulations suggest that the hydrophilic PEO blocks of P188 adsorb at the lipid-water interface while hydrophobic PPO penetrates into the lipid bilayer 28 . Although the previous studies provide some information, direct evidence as to whether P188 and PEO adhere to the lipid membrane is still lacking.…”

Poloxamer 188 Protects Isolated Adult Mouse Cardiomyocytes from Reoxygenation Injury

“…When copolymers like P188 are in solution, they exist as a dynamic population of grouped micelles and single molecules. It has been proposed that the single molecules of P188 in solution are most likely to confer protection compared to grouped P188 micelles because the molecule's hydrophobic portion is more readily available for insertion into, and interaction with, the damaged section of the membrane, as indicated by X‐ray scattering, atomic force microscopy, and computer simulations 16‐18 . It is possible that there were insufficient individual molecules available to provide adequate protection in the assessed cellular parameters when lower concentrations of P188 (eg, 10 µmol/L, 30 µmol/L) were used.…”

“…Poloxamer 188 (P188) is a flexible tri‐block CCMS composed of single bonds and a central hydrophobic 30 PPO unit chain that covalently connects two hydrophilic 75 PEO unit chains (Figure 1A), making P188 ~ 20% hydrophobic with an average MW of 8400 g/mol 14,15 . Through work using X‐ray scattering, atomic force microscopy, and computer simulations, it is thought that P188 directly seals and stabilizes cell membranes by inserting the hydrophobic portion into damaged areas of the membrane while the hydrophilic chains interact with the lipid headgroups of the bilayer and remain at the surface of the membrane, ultimately closing the tear 16‐18 …”

Nanoformulation-by-design: an experimental and molecular dynamics study for polymer coated drug nanoparticles

“…MD in particular has been used to calculate solubility parameters, [47][48][49] polymer-drug encapsulation 46,50 and polymer self-assembly. 43,[51][52][53][54] Through such studies, MD has provided invaluable insight into the interactions that take place at an atomic level, and so link fundamental principles of physics and chemistry to the emergent behaviour of these complex systems. To date however, nanoprecipitation in particular has been modelled most usually using lower resolution computational methods, due to the large size of the systems to be simulated, and long timescales required; dissipative particle dynamics 34,55 is a popular approach.…”