Biophysical perturbations induced by ethylazinphos in lipid membranes

Videira, Romeu A.; Antunes-Madeira, M.C.; Madeira, Vı́tor M.C.

doi:10.1016/s0009-3084(98)00105-4

Cited by 23 publications

(32 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This indicates a strong insertion of C12GEM within the DPPC membrane due to strong hydrophobic interactions as observed for other drugs [34][35][36][37][38]. This phenomenon persisted in the presence of conjugated HA of both molecular weights.…”

Section: Differential Scanning Calorimetry (Dsc)supporting

confidence: 60%

Hyaluronic acid-coated liposomes for active targeting of gemcitabine

Berlier

Lerda

Pozza

et al. 2013

European Journal of Pharmaceutics and Biopharmaceutics

129

View full text Add to dashboard Cite

The aim of this work was the preparation, characterization and preliminary evaluation of the targeting ability towards pancreatic adenocarcinoma cells of liposomes containing the gemcitabine lipophilic prodrug [4-(N)-lauroyl-gemcitabine, C12GEM]. Hyaluronic acid (HA) was selected as targeting agent since it is biodegradable, biocompatible, can be chemically modified and its cell surface receptor CD44 is overexpressed on various tumors.For this purpose, conjugates between a phospholipid, the 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), and HA of two different low molecular weights 4800 Da (12 disaccharidic units) and 12000 Da (32 disaccharidic units), were prepared, characterized and introduced in the liposomes during the preparation.Different liposomal formulations were prepared and their characteristics were analyzed: size, Z potential and TEM analyses underline a difference of the HA-liposomes from the non-HA ones. In order to better understand the HA-liposome cellular localization and to evaluate their interaction with CD44 receptor, confocal microscopy studies were performed. The results demonstrate that HA facilitates the recognition of liposomes by MiaPaCa2 cells (CD44 + ) and that the uptake increases with increasing of the polymer molecular weight.Finally, the cytotoxicity of the different preparations was evaluated and data show that incorporation of C12GEM increases their cytotoxic activity and that HA-liposomes inhibit cell growth more than plain liposomes.Altogether the results demonstrate the specificity of C12GEM targeting towards CD44-overexpressing pancreatic adenocarcinoma cell line using HA as a ligand.

show abstract

Section: Differential Scanning Calorimetry (Dsc)supporting

confidence: 60%

Hyaluronic acid-coated liposomes for active targeting of gemcitabine

Berlier

Lerda

Pozza

et al. 2013

European Journal of Pharmaceutics and Biopharmaceutics

129

View full text Add to dashboard Cite

show abstract

“…Multi-lamellar vesicles (MLVs) were prepared from DPPC according to a standard procedure, 11 derived from the solvent evaporation method originally described in ref. 34.…”

Section: Preparation Of Liposomesmentioning

confidence: 99%

“…This procedure does not affect the transitions of lipid bilayers, but decreases the scattered light, therefore improving fluorescence measurements. 11,35 For these fluorescence studies, in order to obtain a probe/lipid molar ratio of about 1/400, a few microliters of the fluorescent probes dissolved in dimethylformamide were injected into the solution of liposomes (using an Hamilton 10 µl syringe) maintained above the T m of DPPC under vigorous vortexing conditions. Using the same procedure, ALA and ALE surfactants from concentrated aqueous solutions were slowly incorporated in the membrane suspensions.…”

Section: Preparation Of Liposomesmentioning

confidence: 99%

“…Both techniques have been widely employed in studies of interactions relevant to liposome model systems. [10][11][12] DSC provides a systematic tool for assessing the thermodynamic properties of the system, and allows inspection of the respective phase transitions. In turn, fluorescence anisotropy, including the use of a series of fluorescent probes, is used to establish the gradient of order across the bilayer thickness under the influence of the surfactants.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Interaction of arginine-based cationic surfactants with membranes. An experimental and molecular simulation study

Almeida¹,

Morán²,

Infante³

et al. 2009

Arkivoc

View full text Add to dashboard Cite

This work is dedicated to Prof. António M. d'A. Rocha Gonçalves, on the occasion of his 70 th birthday: to the teacher, scientist and academic AbstractThe effect of two arginine-based cationic surfactants, arginine N-lauroyl amide dihydrochloride and arginine O-lauroyl ester dihydrochloride, upon dipalmitoylphosphatidylcholine liposomes, is addressed in this work. Some aspects concerning the synthesis of these surfactants are also presented in some detail. Differential scanning calorimetry, as well as fluorescence anisotropy using several probes, is used to assess the relative effects on the lipid model membranes. In spite of the structural similarity among these molecules, which differ only by the group that connects the polar head to the tail, experimental results suggest differences in their behavior. Molecular dynamics simulation provides significant insight into the molecular mechanism that governs this interaction. A rationale is provided in terms of lipid-surfactant hydrogen bonding and the consequent positioning of the surfactant molecule within the bilayer.

show abstract

“…Examples of the above compounds include anesthetics, calcium channel blocking drugs, alcohols, and insecticides (Makriyannis et al, 1986;Bae et al, 1989;Barry and Gawrisch, 1994;Mavromoustakos et al, 1995;Antunes-Madeira et al, 1996). In particular, the influence of organochlorine and organophosphorus insecticides on the physical properties of lipid bilayers and implications at the level of membrane cell function have been studied in our laboratory (Antunes-Madeira and Madeira, 1993; AntunesMadeira et al, 1994 AntunesMadeira et al, , 1996Videira et al, 1996Videira et al, , 1999aLopes et al, 1997;Donato et al, 1997).It is largely accepted that the basic mechanism of acute toxicity of organophosphorus compounds is associated with the specific inhibition of acetylcholinesterase (Ohkawa, 1982). However, the current understanding of how these compounds interact with the acetylcholinesterase is incomplete (Kardos and Sultatos, 2000), since the capacity to phosphorylate the enzyme appears to decrease as the organophosphorus concentration increases.…”

mentioning

confidence: 99%

Ethylazinphos Interaction with Membrane Lipid Organization Induces Increase of Proton Permeability and Impairment of Mitochondrial Bioenergetic Functions

Videira

Antunes-Madeira

Madeira

2001

Toxicology and Applied Pharmacology

Self Cite

View full text Add to dashboard Cite

Ethylazinphos increases the passive proton permeability of lipid bilayers reconstituted with dipalmitoylphosphatidylcholine (DPPC) and mitochondrial lipids. A sharp increase of proton permeability is detected at insecticide/lipid molar ratios identical to those inducing phase separation in the plane of DPPC bilayers, as revealed by differential scanning calorimetry (DSC). Ethylazinphos progressively depresses the transmembrane potential (⌬⌿) of mitochondria supported by piruvate/malate, succinate, or ascorbate/TMPD. Additionally, a decreased depolarization induced by ADP depends on ethylazinphos concentration, reflecting a phosphorylation depression. This loss of phosphorylation is a consequence of a decreased ⌬⌿. A decreased respiratory control ratio is also observed, since ethylazinphos stimulates state 4 respiration and inhibits ADPstimulated respiration (state 3). Ethylazinphos concentrations up to 100 nmol/mg mitochondrial protein increase the rate of state 4 together with a decrease in ⌬⌿, without significant perturbation of state 3 and carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP)-uncoupled respiration. For increased insecticide concentrations, the state 3 and FCCP-uncoupled respiration are inhibited to approximately the same extent. The perturbations are more pronounced when the energization is supported by pyruvate/ malate and less effective when succinate is used as substrate. The present data, in association with previous DSC studies, indicate that ethylazinphos, at concentrations up to 100 nmol/mg mitochondrial protein, interacts with the lipid bilayer of mitochondrial membrane, changing the lipid organization and increasing the proton permeability of the inner membrane. The increased proton permeability explains the decreased oxidative phosphorylation coupling. Resulting disturbed ATP synthesis may significantly underlie the mechanisms of ethylazinphos toxicity, since most of cell energy in eukaryotes is provided by mitochondria. © 2001 Academic PressKey Words: ethylazinphos; membrane organization; proton permeability; mitochondrial respiration; transmembrane potential; oxidative phosphorylation.The two major components of the biological membranes are lipids and proteins. Together they determine the organization and function of membranes. These dynamic and versatile barriers are, in turn, involved in most cellular functions (Kinnunen, 1991). A large number of drugs with different chemical structures and pharmacological effects are able to accumulate in membrane lipid domains, changing their organization and physical properties and, consequently, their function (Sikkema et al., 1995;Mouritsen and Jørgensen, 1998), since the preservation of an exact degree of organization is essential for most membrane activities (Eze, 1990;Mouritsen and Jørgensen, 1998;Williams, 1998). Examples of the above compounds include anesthetics, calcium channel blocking drugs, alcohols, and insecticides (Makriyannis et al., 1986;Bae et al., 1989;Barry and Gawrisch, 1994;Mavromoustakos et al., 1995;Antunes-Madeira...

show abstract

Biophysical perturbations induced by ethylazinphos in lipid membranes

Cited by 23 publications

References 56 publications

Hyaluronic acid-coated liposomes for active targeting of gemcitabine

Hyaluronic acid-coated liposomes for active targeting of gemcitabine

Interaction of arginine-based cationic surfactants with membranes. An experimental and molecular simulation study

Ethylazinphos Interaction with Membrane Lipid Organization Induces Increase of Proton Permeability and Impairment of Mitochondrial Bioenergetic Functions

Contact Info

Product

Resources

About