Effects of ethanol/l-menthol on the dynamics and partitioning of spin-labeled lipids in the stratum corneum

Anjos, Jorge Luiz Vieira dos; Neto, Diógenes de Sousa; Alonso, Antônio

doi:10.1016/j.ejpb.2007.02.004

Cited by 37 publications

(31 citation statements)

References 26 publications

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“…The efficiency of incorporation and the uniformity of the probe distribution throughout the membrane can be verified on the basis of the EPR spectra immediately after labeling. For instance, spin-labeled lipids have been successfully incorporated into stratum corneum membranes (20), cellular membranes of coffee root tip segments (21), Trypanosoma cruzi protozoans (22), and fibroblasts (23). EPR spectroscopy has identified the presence of two populations of spin labels differing in molecular dynamics in cell membranes (24).…”

Section: Discussionmentioning

confidence: 99%

Miltefosine Increases Lipid and Protein Dynamics in Leishmania amazonensis Membranes at Concentrations Similar to Those Needed for Cytotoxicity Activity

Moreira

Mendanha

Fernandes

et al. 2014

Antimicrob Agents Chemother

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b Miltefosine (MT) is a membrane-active alkylphospholipid licensed for the topical treatment of breast cancer skin metastases and the oral treatment of leishmaniasis, although its mechanism of action remains unclear. Electron paramagnetic resonance (EPR) spectroscopy of a spin-labeled lipid and a thiol-specific spin label in the plasma membrane of Leishmania promastigotes showed that MT causes dramatic increases in membrane dynamics. Although these alterations can be detected using a spin-labeled lipid, our experimental results indicated that MT interacts predominantly with the protein component of the membrane. Cell lysis was also detected by analyzing the supernatants of centrifuged samples for the presence of spin-labeled membrane fragments and cytoplasmic proteins. Using a method for the rapid incorporation of MT into the membrane, these effects were measured immediately after treatment under the same range of MT concentrations that cause cell growth inhibition. Cytotoxicity, estimated via microscopic counting of living and dead cells, indicated ϳ70% cell death at the concentration of MT at which EPR spectroscopy detected a significant change in membrane dynamics. After this initial impact on the number of viable parasites, the processes of cell death and growth continued during the first 4 h of incubation. The EPR spectra of spin-labeled membrane-bound proteins were consistent with more expanded and solvent-exposed protein conformations, suggesting a detergent-like action. Thus, MT may form micelle-like structures around polypeptide chains, and proteins with a higher hydrophobicity may induce the penetration of hydrophilic groups of MT into the membrane, causing its rupture. L eishmaniasis is caused by protozoan parasites of over 20 Leishmania species and is transmitted to humans via the bite of infected female sand flies. There are three main types of leishmaniasis: cutaneous (the most common form), visceral (the most severe clinical manifestation, which is fatal if untreated), and mucocutaneous. According to a recent report from the World Health Organization (WHO) (1), there are an estimated 1.3 million new cases of leishmaniasis worldwide and an estimated 20,000 to 30,000 deaths caused by these parasites annually.Miltefosine (MT) was the first oral drug approved for use for the treatment of visceral and cutaneous leishmaniasis and is currently registered for leishmaniasis treatment in India (2002, as Impavido), Germany (2004), and Colombia (2005) (2). This drug is also used clinically for the topical treatment of skin metastases associated with breast cancer and cutaneous lymphoma (3). MT has shown high cure rates in the treatment of visceral (4), cutaneous (5), and mucocutaneous (6) leishmaniasis. Although many studies have been conducted to identify the mechanisms underlying the action of MT against tumor cells (3) and parasites (7), these mechanisms have not yet been determined. However, due to its chemical structure, which provides MT with a high membrane affinity, the primary molecular targets of MT...

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Section: Discussionmentioning

confidence: 99%

Miltefosine Increases Lipid and Protein Dynamics in Leishmania amazonensis Membranes at Concentrations Similar to Those Needed for Cytotoxicity Activity

Moreira

Mendanha

Fernandes

et al. 2014

Antimicrob Agents Chemother

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“…Recent studies conducted by Heard revealed that enhancement of mefenamic acid using 1,8-cineole was due to "drag" or "pull" effect (51). However, another study suggested intercalation of cineole into lipids and proteins by forming hydrogen bonds thus, altering the organization of SC (52).…”

Section: Cineolementioning

confidence: 99%

Percutaneous Permeation Enhancement by Terpenes: Mechanistic View

Sapra

Jain

Tiwary

2008

AAPS J

145

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Abstract. A popular approach for improving transdermal drug delivery involves the use of penetration enhancers (sorption promoters or accelerants) which penetrate into skin to reversibly reduce the barrier resistance. The potential mechanisms of action of penetration enhancers include disruption of intercellular lipid and/or keratin domains and tight junctions. This results in enhanced drug partitioning into tissue, altered thermodynamic activity/solubility of drug etc. Synthetic chemicals (solvents, azones, pyrrolidones, surfactants etc.) generally used for this purpose are rapidly losing their value in transdermal patches due to reports of their absorption into the systemic circulation and subsequent possible toxic effect upon long term application. Terpenes are included in the list of Generally Recognized As Safe (GRAS) substances and have low irritancy potential. Their mechanism of percutaneous permeation enhancement involves increasing the solubility of drugs in skin lipids, disruption of lipid/protein organization and/or extraction of skin micro constituents that are responsible for maintenance of barrier status. Hence, they appear to offer great promise for use in transdermal formulations. This article is aimed at reviewing the mechanisms responsible for percutaneous permeation enhancement activity of terpenes, which shall foster their rational use in transdermal formulations.

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“…6 In previous studies, two-component EPR spectra of several spin labels in membranes of stratum corneum, the upper skin layer, were examined using the fitting program NLLS to monitor the dynamic and fraction of probe in each component. [8][9][10] The presence of the terpenes L-menthol and 1,8-cineole, two potent skin permeation enhancers, in stratum corneum at 1% (w/w) or DPPC vesicles at a terpene:lipid molar ratio of 0.7:1 drastically increased the lipid fluidity, especially by transferring the spin probes from a more to a less motionally restricted spectral component in the membranes. 9,10 More recently, EPR spectra of spin labels in membrane were simulated using two-component models to study effects of the anti antileishmanial drug miltefosine in stratum corneum intercellular membranes 11 and trypanocidal action of elatol 12 as well as the toxicity of terpenes in cultured fibroblasts.…”

Section: Introductionmentioning

confidence: 99%

“…[8][9][10] The presence of the terpenes L-menthol and 1,8-cineole, two potent skin permeation enhancers, in stratum corneum at 1% (w/w) or DPPC vesicles at a terpene:lipid molar ratio of 0.7:1 drastically increased the lipid fluidity, especially by transferring the spin probes from a more to a less motionally restricted spectral component in the membranes. 9,10 More recently, EPR spectra of spin labels in membrane were simulated using two-component models to study effects of the anti antileishmanial drug miltefosine in stratum corneum intercellular membranes 11 and trypanocidal action of elatol 12 as well as the toxicity of terpenes in cultured fibroblasts. 13 Since the question of the spectral components in the EPR spectra of spin-labeled lipids in membrane models of simple bilayers has not been addressed in depth, we conducted an extensive experimental study with the spin probe methyl 5-doxyl-stearate (5-DMS) in vesicles of saturated phosphatidylcholines with acyl chain lengths ranging from 16 to 22 carbon atoms and temperatures in the 10 to 78 o C range.…”

Section: Introductionmentioning

confidence: 99%

Electron paramagnetic resonance (EPR) spectral components of spin-labeled lipids in saturated phospholipid bilayers: effect of cholesterol

Camargos¹,

Alonso²

2013

Quím. Nova

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Recebido em 23/9/12; aceito em 7/1/13; publicado na web em 6/5/13Electron paramagnetic resonance (EPR) spectroscopy was used to study the main structural accommodations of spin labels in bilayers of saturated phosphatidylcholines with acyl chain lengths ranging from 16 to 22 carbon atoms. EPR spectra allowed the identification of two distinct spectral components in thermodynamic equilibrium at temperatures below and above the main phase transition. An accurate analysis of EPR spectra, using two fitting programs, enabled determination of the thermodynamic profile for these major probe accommodations. Focusing the analysis on two-component EPR spectra of a spin-labeled lipid, the influence of 40 mol % cholesterol in DPPC was studied.

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Effects of ethanol/l-menthol on the dynamics and partitioning of spin-labeled lipids in the stratum corneum

Cited by 37 publications

References 26 publications

Miltefosine Increases Lipid and Protein Dynamics in Leishmania amazonensis Membranes at Concentrations Similar to Those Needed for Cytotoxicity Activity

Miltefosine Increases Lipid and Protein Dynamics in Leishmania amazonensis Membranes at Concentrations Similar to Those Needed for Cytotoxicity Activity

Percutaneous Permeation Enhancement by Terpenes: Mechanistic View

Electron paramagnetic resonance (EPR) spectral components of spin-labeled lipids in saturated phospholipid bilayers: effect of cholesterol

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