Study of Interaction Between PEG Carrier and Three Relevant Drug Molecules: Piroxicam, Paclitaxel, and Hematoporphyrin

Li, Yen-Chin; Rissanen, Sami; Stȩpniewski, Michał; Cramariuc, Oana; Róg, Tomasz; Mirza, Sabir; Xhaard, Henri; Wytrwał-Sarna, Magdalena; Kępczyński, Mariusz; Bunker, Alex

doi:10.1021/jp300301z

Cited by 54 publications

(53 citation statements)

References 51 publications

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“…It is noteworthy that although PEG is commonly used in block copolymers as hydrophilic moiety, it is soluble in both water and organic solvents owing to the hydrophobic nature of the ethylene groups. Although few examples are known in the literature, PEG polymers have proven their ability to interact with hydrophobic drugs [45]. …”

Section: Resultsmentioning

confidence: 99%

PEGylated versus non-PEGylated magnetic nanoparticles as camptothecin delivery system

Castillo¹,

Mata²,

Casula³

et al. 2014

Beilstein J. Nanotechnol.

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SummaryCamptothecin (CPT; (S)-(+)-4-ethyl-4-hydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-(4H,12H)-dione) is a highly cytotoxic natural alkaloid that has not yet found use as chemotherapeutic agent due to its poor water-solubility and chemical instability and, as a consequence, no effective administration means have been designed. In this work, camptothecin has been successfully loaded into iron oxide superparamagnetic nanoparticles with an average size of 14 nm. It was found that surface modification of the nanoparticles by polyethylene glycol enables loading a large amount of camptothecin. While the unloaded nanoparticles do not induce apoptosis in the H460 lung cancer cell line, the camptothecin-loaded nanoparticle formulations exhibit remarkable pro-apoptotic activity. These results indicate that camptothecin retains its biological activity after loading onto the magnetic nanoparticles. The proposed materials represent novel materials based on naturally occurring bioactive molecules loaded onto nanoparticles to be used as chemotherapeutic formulations. The procedure seems apt to be extended to other active molecules extracted from natural products. In addition, these materials offer the potential of being further implemented for combined imaging and therapeutics, as magnetic nanoparticles are known to be multifunctional tools for biomedicine.

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Section: Resultsmentioning

confidence: 99%

PEGylated versus non-PEGylated magnetic nanoparticles as camptothecin delivery system

Castillo¹,

Mata²,

Casula³

et al. 2014

Beilstein J. Nanotechnol.

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“…In our previous studies we showed that increasing PEG concentration causes the aggregation of hemotoporphyrin to decrease. 32 The FQA experiments were performed to validate the results of the computer simulations. For POPC membranes, the efficiency of quenching by copper cations is low.…”

Section: Discussionmentioning

confidence: 99%

PEGylated Liposomes as Carriers of Hydrophobic Porphyrins

et al. 2015

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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.

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“…The receptor grid was generated using a 1.0 van der Waals radius scaling factor, 0.25 partial charge cut-off without any constraint [18]. Partial charges for the ligand atoms were obtained from the OPLS-AA force field [19], which do not reflect the influence of the environment on the atomic charges. The location of taxol in both complexes was taken as a binding site for docking of all the ligands.…”

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confidence: 99%

Stabilization of Microtubules by Taxane Diterpenoids: Insight from Docking and MD simulations

2014

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Microtubules are formed from the molecules of tubulin, whose dynamics is important for many functions in a cell, the most dramatic of which is mitosis. Taxol is known to interact within a specific site on tubulin and also believed to block cell-cycle progression during mitosis by binding to and stabilizing microtubules. Along with the tremendous potential that taxol has shown as an anticancer drug, clinical problems exist with solubility, toxicity, and development of drug resistance. The crystal structure of taxane diterpenoids, namely, 10, 13-deacetyl-abeo-baccatin-IV (I), 5-acetyl-2-deacetoxydecinnamoyl-taxinine-0.29hydrate (II), 7, 9-dideacetyltaxayuntin (III), and Taxawallin-K (IV), are very similar to the taxol molecule. Considerable attention has been given to such molecules whose archetype is taxol but do not posses long aliphatic chains, to be developed as a substitute for taxol with fewer side effects. In the present work, the molecular docking of these taxane diterpenoids has been carried out with the tubulin alpha-beta dimer (1TUB) and refined microtubule structure (1JFF) using Glide-XP, in order to assess the potential of tubulin binding of these cytotoxic agents. Results show that all the ligands dock into the classical taxol binding site of tubulin. Taxol shows the best binding capabilities. On the basis of docking energy and interactions, apart from taxol, molecule II has a better tendency of binding with 1TUB while molecule I shows better binding capability with bovine tubulin 1JFF. To validate the binding capabilities, molecular dynamics (MD) simulations of the best docked complexes of ligands with 1JFF have been carried out for 15.0 ns using DESMOND. Average RMSD variations and time line study of interactions and contacts indicate that these complexes remain stable during the course of the dynamics. However, taxol and molecule II prevail over other taxoids.

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Study of Interaction Between PEG Carrier and Three Relevant Drug Molecules: Piroxicam, Paclitaxel, and Hematoporphyrin

Cited by 54 publications

References 51 publications

PEGylated versus non-PEGylated magnetic nanoparticles as camptothecin delivery system

PEGylated versus non-PEGylated magnetic nanoparticles as camptothecin delivery system

PEGylated Liposomes as Carriers of Hydrophobic Porphyrins

Stabilization of Microtubules by Taxane Diterpenoids: Insight from Docking and MD simulations

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