Effect of PEGylation on drug entry into lipid bilayer

The Journal of Physical Chemistry. B
Sami RissanenTomasz Róg

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.

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Citations

Oct 1, 2015·The Journal of Physical Chemistry. B·Francesca Stanzione, Arthi Jayaraman
Jul 12, 2016·Langmuir : the ACS Journal of Surfaces and Colloids·Priyanka A OroskarSohail Murad
Feb 25, 2018·Journal of Molecular Modeling·Abbas YousefpourSepideh Amjad-Iranagh
Sep 25, 2017·Biophysics Reviews·Antonio R da CunhaKaline Coutinho
Apr 5, 2016·Journal of Biophotonics·Ashwini A Ghogare, Alexander Greer
Jun 26, 2020·Colloids and Surfaces. B, Biointerfaces·Jafar Rahnama YazdiMahmoud Reza Jaafari
Dec 18, 2020·Frontiers in Molecular Biosciences·Alex Bunker, Tomasz Róg
May 21, 2021·International Journal of Pharmaceutics·Leonidas GkionisAnnalisa Tirella
May 13, 2015·The Journal of Physical Chemistry. B·Monika DzieciuchMariusz Kepczynski
Feb 17, 2015·The Journal of Physical Chemistry. B·Goutam GhoshAlexander Greer
Aug 21, 2021·International Journal of Pharmaceutics·Vera L SilvaWafa' T Al-Jamal

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