title: Effect of PEGylation on drug entry into lipid bilayer.
abstract: Poly(ethylene glycol) (PEG) is a polymer commonly used for functionalization of drug molecules to increase their bloodstream lifetime, hence efficacy. However, the interactions between the PEGylated drugs and biomembranes are not clearly understood. In this study, we employed atomic-scale molecular dynamics (MD) simulations to consider the behavior of two drug molecules functionalized with PEG (tetraphenylporphyrin used in cancer phototherapy and biochanin A belonging to the isoflavone family) in the presence of a lipid bilayer. The commonly held view is that functionalization of a drug molecule with a polymer acts as an entropic barrier, inhibiting the penetration of the drug molecule through a cell membrane. Our results indicate that in the bloodstream there is an additional source of electrostatic repulsive interactions between the PEGylated drugs and the lipid bilayer. Both the PEG chain and lipids can bind Na(+) ions, thus effectively becoming positively charged molecules. This leads to an extra repulsive effect resulting from the presence of salt in the bloodstream. Thus, our study sheds further light on the role of PEG in drug delivery.
authors.affiliation: Department of Physics, Tampere University of Technology , PO Box 692, FI-33101 Tampere, Finland.
authors.forename: Sami
authors.initials: S
authors.lastname: Rissanen
authors.forename: Marta
authors.initials: M
authors.lastname: Kumorek
authors.forename: Hector
authors.initials: H
authors.lastname: Martinez-Seara
authors.forename: Yen-Chin
authors.initials: YC
authors.lastname: Li
authors.forename: Dorota
authors.initials: D
authors.lastname: Jamróz
authors.forename: Alex
authors.initials: A
authors.lastname: Bunker
authors.forename: Maria
authors.initials: M
authors.lastname: Nowakowska
authors.forename: Ilpo
authors.initials: I
authors.lastname: Vattulainen
authors.forename: Mariusz
authors.initials: M
authors.lastname: Kepczynski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Róg
mesh_terms: D019833:Genistein / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D011166:Porphyrins; C409084:tetraphenylporphyrin; D011092:Polyethylene Glycols; D019833:Genistein; C004541:biochanin A