Effect of PEGylation on Drug Entry into Lipid Bilayer

Rissanen, Sami; Kumorek, Marta; Martinez‐Seara, Hector; Li, Yen-Chin; Jamroz, D.; Bunker, Alex; Nowakowska, Maria; Vattulainen, Ilpo; Kępczyński, Mariusz

doi:10.1021/jp4105745

Cited by 26 publications

(22 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Short chain PEG groups, such as [–O(CH 2 CH 2 O) 3 ⋅ CH 3 ] when bonded to sensitizers can reduce self‐aggregation , and retain some propensity to localize in cell membranes compared to unsubstituted sensitizers . Therefore, we surmised that a galloyl unit carrying three PEG groups could be bonded to pheophorbide silica end‐tips of a pointsource PDT device.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of a poly(ethylene glycol) galloyl sensitizer tip for an ’all‐in‐one' photodynamic device

Ghogare

Greer

2016

Journal of Biophotonics

View full text Add to dashboard Cite

This paper describes the synthesis of a specialized silica tip for an optical fiber device capable of delivering all components necessary for photodynamic therapy. Oxygen, light and a cleavable tripolyethylene glycol (PEG)-galloyl pheophorbide sensitizer are simultaneously delivered by the silica tip, where the tip was synthesized in six steps. A comparison of synthetic steps to reach PEGylated sensitizers bound to fluorinated silica and a previously reported Teflon/polyvinyl alcohol (PVA) nanocomposite ( Ghosh, G. et al. J. Phys. Chem. B 2015, 119, 4155- 4164) was made. The hydrolytic stability of the attached PEGs and the extent to which the PEG groups enhance solubility will also be discussed. The new triPEG-galloyl sensitizer has the potential for use in intraoperative pointsource photodynamic therapy which aims for precision treatment of residual disease. Schematic of the synthesis of a photoactive silica surface. It is composed of fluorinated silica connected to a photo-releasable sensitizer with short-chain PEGs.

show abstract

Section: Resultsmentioning

confidence: 99%

Synthesis of a poly(ethylene glycol) galloyl sensitizer tip for an ’all‐in‐one' photodynamic device

Ghogare

Greer

2016

Journal of Biophotonics

View full text Add to dashboard Cite

show abstract

“…On the other hand, we have also shown that the spatial distribution of p-THPP (a tetraarylporphyrin) in a POPC bilayer is more complex. 49 It is characterized by two preferred positions: one at 1.51 nm from the bilayer center, corresponding to a location of the lipid carbonyl groups, and another at 0.81 nm from the bilayer center. To gain more detailed insight into the preferred The Journal of Physical Chemistry B Article arrangement of p-THPP in lipid membranes, here we performed simulations in two different bilayers, namely POPC and DLPC.…”

Section: Discussionmentioning

confidence: 99%

PEGylated Liposomes as Carriers of Hydrophobic Porphyrins

et al. 2015

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…It has been adopted in theoretical studies of biological membrane models (Tieleman et al 1997;Mark 2010, 2012) and partitioning and interaction of drugs in lipid bilayers (Fuchs et al 1990;Omote and Al-Shawi 2006;MacCallum and Tieleman 2006;Bemporad et al 2004). Indeed, MD simulations have contributed significantly to the understanding of the structure, dynamics and effects of biological molecules in lipid bilayers (Seydel and Wiese 2002;Xiang and Anderson 2006;Yamamoto et al 2012;Rissanen et al 2014;Almeida et al 2017). However, due to the variety of classical force fields available, it is important to compare the results obtained from the simulations with the experimental data to validate the simulation force field and protocols.…”

Section: Introductionmentioning

confidence: 99%

Experimental and theoretical studies of emodin interacting with a lipid bilayer of DMPC

et al. 2017

View full text Add to dashboard Cite

Emodin is one of the most abundant anthraquinone derivatives found in nature. It is the active principle of some traditional herbal medicines with known biological activities. In this work, we combined experimental and theoretical studies to reveal information about location, orientation, interaction and perturbing effects of Emodin on lipid bilayers, where we have taken into account the neutral form of the Emodin (EMH) and its anionic/deprotonated form (EM − ). Using both UV/Visible spectrophotometric techniques and molecular dynamics (MD) simulations, we showed that both EMH and EM − are located in a lipid membrane. Additionally, using MD simulations, we revealed that both forms of Emodin are very close to glycerol groups of the lipid molecules, with the EMH inserted more deeply into the bilayer and more disoriented relative to the normal of the membrane when compared with the EM − , which is more exposed to interfacial water. Analysis of several structural properties of acyl chains of the lipids in a hydrated pure DMPC bilayer and in the presence of Emodin revealed that both EMH and EM − affect the lipid bilayer, resulting in a remarkable disorder of the bilayer in the vicinity of the Emodin. However, the disorder caused by EMH is weaker than that caused by EM − . Our results suggest that these disorders caused by Emodin might lead to distinct effects on lipid bilayers including its disruption which are reported in the literature.

show abstract

Effect of PEGylation on Drug Entry into Lipid Bilayer

Cited by 26 publications

References 49 publications

Synthesis of a poly(ethylene glycol) galloyl sensitizer tip for an ’all‐in‐one' photodynamic device

Synthesis of a poly(ethylene glycol) galloyl sensitizer tip for an ’all‐in‐one' photodynamic device

PEGylated Liposomes as Carriers of Hydrophobic Porphyrins

Experimental and theoretical studies of emodin interacting with a lipid bilayer of DMPC

Contact Info

Product

Resources

About