title: PEGylated Liposomes as Carriers of Hydrophobic Porphyrins.
abstract: Sterically stabilized liposomes (SSLs) (PEGylated liposomes) are applied as effective drug delivery vehicles. Understanding the interactions between hydrophobic compounds and PEGylated membranes is therefore important to determine the effectiveness of PEGylated liposomes for delivery of drugs or other bioactive substances. In this study, we have combined fluorescence quenching analysis (FQA) experiments and all-atom molecular dynamics (MD) simulations to study the effect of membrane PEGylation on the location and orientation of 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin (p-THPP) that has been used in our study as a model hydrophobic compound. First, we consider the properties of p-THPP in the presence of different fluid phosphatidylcholine bilayers that we use as model systems for protein-free cell membranes. Next, we studied the interaction between PEGylated membranes and p-THPP. Our MD simulation results indicated that the arrangement of p-THPP within zwitterionic membranes is dependent on their free volume, and p-THPP solubilized in PEGylated liposomes is localized in two preferred positions: deep within the membrane (close to the center of the bilayer) and in the outer PEG corona (p-THPP molecules being wrapped with the polymer chains). Fluorescence quenching methods confirmed the results of atomistic MD simulations and showed two populations of p-THPP molecules as in MD simulations. Our results provide both an explanation for the experimental observation that PEGylation improves the drug-loading efficiency of membranes and also a more detailed molecular-level description of the interactions between porphyrins and lipid membranes.
authors.affiliation: †Faculty of Chemistry, Jagiellonian University, Krakow 31-007, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Dzieciuch
authors.affiliation: ‡Department of Physics, Tampere University of Technology, Tampere 33720, Finland.
authors.forename: Sami
authors.initials: S
authors.lastname: Rissanen
authors.affiliation: †Faculty of Chemistry, Jagiellonian University, Krakow 31-007, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Szydłowska
authors.affiliation: §Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, Helsinki 00100, Finland.
authors.forename: Alex
authors.initials: A
authors.lastname: Bunker
authors.affiliation: †Faculty of Chemistry, Jagiellonian University, Krakow 31-007, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Kumorek
authors.affiliation: †Faculty of Chemistry, Jagiellonian University, Krakow 31-007, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Jamróz
authors.affiliation: ‡Department of Physics, Tampere University of Technology, Tampere 33720, Finland.|∥MEMPHYS-Center for Biomembrane Physics, University of Southern Denmark, Odense 5230, Denmark.
authors.forename: Ilpo
authors.initials: I
authors.lastname: Vattulainen
authors.affiliation: †Faculty of Chemistry, Jagiellonian University, Krakow 31-007, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Nowakowska
authors.affiliation: ‡Department of Physics, Tampere University of Technology, Tampere 33720, Finland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Róg
authors.affiliation: †Faculty of Chemistry, Jagiellonian University, Krakow 31-007, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Kepczynski
mesh_terms: D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes / Q000737:chemistry*; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D011092:Polyethylene Glycols / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
chemical_list: D008081:Liposomes; D011166:Porphyrins; D011092:Polyethylene Glycols; C051232:5,10,15,20-tetra(4-hydroxyphenyl)porphyrin