PEGylated liposomes as carriers of hydrophobic porphyrins

Sterically stabilized liposomes (SSLs) (PEGylated liposomes) are applied as e ff ective drug delivery vehicles. Under- standing the interactions between hydrophobic compounds and PEGylated membranes is therefore important to determine the e ff ectiveness of PEGylated liposomes for delivery of drugs or other bioactive substances. In this study, we have combined fl uorescence quenching analysis (FQA) experiments and all-atom molecular dynamics (MD) simulations to study the e ff ect 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 di ff erent fl uid 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 con fi rmed 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 e ffi ciency of membranes and also a more detailed molecular-level description of the interactions between porphyrins and lipid membranes