Effect of tetracaine on DMPC and DMPC+cholesterol biomembrane models: Liposomes and monolayers

Abstract

Different types of lipid bilayers/monolayers have been used to simulate the cellular membranes in the investigation of the interactions between drugs and cells. However, to our knowledge, very few studies focused on the influence of the chosen membrane model upon the obtained results. The main objective of this work is to understand how do the nature and immobilization state of the biomembrane models influence the effect of the local anaesthetic tetracaine (TTC) upon the lipid membranes. The interaction of TTC with different biomembrane models of dimyristoylphosphatidylcholine (DMPC) with and without cholesterol (CHOL) was investigated through several techniques. A quartz crystal microbalance with dissipation (QCM-D) was used to study the effect on immobilized liposomes, while phosphorus nuclear magnetic resonance ( 31 P-NMR) and differential scanning calorimetry (DSC) were applied to liposomes in suspension. The effect of TTC on Langmuir monolayers of lipids was also investigated through surface pressure-area measurements at the air-water interface. The general conclusion was that TTC has a fluidizing effect on the lipid membranes and, above certain concentrations, induced membrane swelling or even solubilization. However, different models led to variable responses to the TTC action. The intensity of the disordering effect caused by TTC increased in the following order: supported liposomes < liposomes in solution < Langmuir monolayers. This means that extrapolation of the results obtain in in vitro studies of the lipid/anaesthetic interactions to in vivo conditions should be done carefully.

Interactions of bioactive molecules & nanomaterials with Langmuir monolayers as cell membrane models

“…Similar results were obtained for tetracaine and lidocaine hydrochlorides, penetrating DPPC and DMPE monolayers [224,225] as well as mixed DMPC-cholesterol films [225], and procaine [226], which -after being dissolved in water -are incorporated into the stearic acid monolayer, chosen as a model lipid…”

“…Typical examples include: antimicrobials [117,, anti-tumorals [116,, antiinflammatory [77,[214][215][216][217], anesthesics [218][219][220][221][222][223][224][225][226][227], anti-psychotics [228][229][230][231][232][233][234][235][236][237], cardiac [238][239][240][241][242][243][244][245] and antihistaminic [246] drugs. To address this issue, Langmuir monolayers have been used involving AmB alone as well as mixed with membrane sterols.…”

Effects of triglycerides on the hydrophobic drug loading capacity of saturated phosphatidylcholine-based liposomes

“…1A). It has been reported that incorporation of CHOL between PC molecules disrupts the packing order of gel-phase bilayers, consequently reducing the main T m of saturated PC vehicles (McMullen et al, 1993;Serro et al, 2014). Addition of tributyrin into the DMPC: CHOL mixture slightly sharpened the phase-transition peak without affecting the phase-transition temperature.…”

Distribution of Xanthene Dyes in DPPC Vesicles: Rationally Accounting for Drug Partitioning Using a Membrane Model

“…These changes occur because of the loss of hydrogen bonding when the dyes are not in protic solvents and, consequently, the HOMO-LUMO (highest occupied molecular orbital-lowest unoccupied molecular orbital) gap becomes smaller. 9 Additionally, the higher fluorescence intensities of the dyes observed in DPPC compared to water is probably due to the decrease in the vibrational deactivation route. 21 Determination of binding constants, fluorescence anisotropy, and molecular properties Figure 3a presents the variation in the fluorescence emission spectrum of ERY upon titration with the phospholipids.…”

“…7,8 The complexity of biological membranes makes direct studies very difficult; thus, simple model systems that can mimic the cellular environment, such as micelles and lipid vesicles, have been used. [9][10][11] Lipid vesicles are concentric uni-or multilamellar lipid bilayers that have layer diameters Vol. 27, No.…”