scholarly journals Comparison of the interactions of daunorubicin in a free form and attached to single-walled carbon nanotubes with model lipid membranes

2016 ◽  
Vol 7 ◽  
pp. 524-532 ◽  
Author(s):  
Dorota Matyszewska

In this work the interactions of an anticancer drug daunorubicin (DNR) with model thiolipid layers composed of 1,2-dipalmitoyl-sn-glycero-3-phosphothioethanol (DPPTE) were investigated using Langmuir technique. The results obtained for a free drug were compared with the results recorded for DNR attached to SWCNTs as potential drug carrier. Langmuir studies of mixed DPPTE–SWCNTs-DNR monolayers showed that even at the highest investigated content of the nanotubes in the monolayer, the changes in the properties of DPPTE model membranes were not as significant as in case of the incorporation of a free drug, which resulted in a significant increase in the area per molecule and fluidization of the thiolipid layer. The presence of SWCNTs-DNR in the DPPTE monolayer at the air–water interface did not change the organization of the lipid molecules to such extent as the free drug, which may be explained by different types of interactions playing crucial role in these two types of systems. In the case of the interactions of free DNR the electrostatic attraction between positively charged drug and negatively charged DPPTE monolayer play the most important role, while in the case of SWCNTs-DNR adducts the hydrophobic interactions between nanotubes and acyl chains of the lipid seem to be prevailing. Electrochemical studies performed for supported model membranes containing the drug delivered in the two investigated forms revealed that the surface concentration of the drug-nanotube adduct in supported monolayers is comparable to the reported surface concentration of the free DNR incorporated into DPPTE monolayers on gold electrodes. Therefore, it may be concluded that the application of carbon nanotubes as potential DNR carrier allows for the incorporation of comparable amount of the drug into model membranes with simultaneous decrease in the negative changes in the membrane structure and organization, which is an important aspect in terms of side effects of the drug.

Membranes ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 319
Author(s):  
Joyce El-Beyrouthy ◽  
Eric Freeman

The cell membrane is a protective barrier whose configuration determines the exchange both between intracellular and extracellular regions and within the cell itself. Consequently, characterizing membrane properties and interactions is essential for advancements in topics such as limiting nanoparticle cytotoxicity. Characterization is often accomplished by recreating model membranes that approximate the structure of cellular membranes in a controlled environment, formed using self-assembly principles. The selected method for membrane creation influences the properties of the membrane assembly, including their response to electric fields used for characterizing transmembrane exchanges. When these self-assembled model membranes are combined with electrophysiology, it is possible to exploit their non-physiological mechanics to enable additional measurements of membrane interactions and phenomena. This review describes several common model membranes including liposomes, pore-spanning membranes, solid supported membranes, and emulsion-based membranes, emphasizing their varying structure due to the selected mode of production. Next, electrophysiology techniques that exploit these structures are discussed, including conductance measurements, electrowetting and electrocompression analysis, and electroimpedance spectroscopy. The focus of this review is linking each membrane assembly technique to the properties of the resulting membrane, discussing how these properties enable alternative electrophysiological approaches to measuring membrane characteristics and interactions.


1994 ◽  
Vol 14 (1) ◽  
pp. 15-24 ◽  
Author(s):  
João Ramalho-Santos ◽  
Ricardo Negrão ◽  
Maria da Conceição Pedroso de Lima

We have studied the role of hydrophobic interactions in the fusion activity of two lipid enveloped viruses, influenza and Sendai. Using the fluorescent probe ANS (1-aminonaphtalene-8-sulfonate) we have shown that low-pH-dependent influenza virus activation involves a marked increase in the viral envelope hydrophobicity. The effect of dehydrating agents on the fusion activity of both viruses towards model lipid membranes was studied using a fluorescence dequenching assay. Dehydrating agents such as dimethylsulfoxide and dimethylsulfone greatly enhanced the initial rate of the fusion process, the effect of dimethylsulfone doubling that of dimethylsulfoxide. The effect of poly(ethylene glycol) on the fusion process was found to be dependent on the polymer concentration and molecular weight. In general, similar observations were made for both viruses. These results stress the importance of dehydration and hydrophobic interactions in the fusion activity of influenza and Sendai viruses, and show that these factors may be generally involved in membrane fusion events mediated by many other lipid enveloped viruses.


2021 ◽  
Vol 22 (18) ◽  
pp. 10085
Author(s):  
Aritz B. García-Arribas ◽  
Félix M. Goñi ◽  
Alicia Alonso

Lipid model membranes are important tools in the study of biophysical processes such as lipid self-assembly and lipid–lipid interactions in cell membranes. The use of model systems to adequate and modulate complexity helps in the understanding of many events that occur in cellular membranes, that exhibit a wide variety of components, including lipids of different subfamilies (e.g., phospholipids, sphingolipids, sterols…), in addition to proteins and sugars. The capacity of lipids to segregate by themselves into different phases at the nanoscale (nanodomains) is an intriguing feature that is yet to be fully characterized in vivo due to the proposed transient nature of these domains in living systems. Model lipid membranes, instead, have the advantage of (usually) greater phase stability, together with the possibility of fully controlling the system lipid composition. Atomic force microscopy (AFM) is a powerful tool to detect the presence of meso- and nanodomains in a lipid membrane. It also allows the direct quantification of nanomechanical resistance in each phase present. In this review, we explore the main kinds of lipid assemblies used as model membranes and describe AFM experiments on model membranes. In addition, we discuss how these assemblies have extended our knowledge of membrane biophysics over the last two decades, particularly in issues related to the variability of different model membranes and the impact of supports/cytoskeleton on lipid behavior, such as segregated domain size or bilayer leaflet uncoupling.


2000 ◽  
Vol 55 (9-10) ◽  
pp. 764-769
Author(s):  
Halina Kleszczyńska ◽  
Krzysztof Bielecki ◽  
Janusz Sarapuk ◽  
Anna Dziamska ◽  
Stanislaw Przestalski

Abstract The physiological and hemolytic toxicities of triphenyllead chloride (TPhL) as well as its modyfying influence on model lipid membranes were studied. The experiments allowed the determination of TPhL concentrations causing 50% inhibition of growth of Spirodela oligorrhiza, Lemna minor and Solvinia natans (EC50), 100% hemolysis of pig erythrocytes (C100) and destabilization of planar lipid membranes (CC). Also, fluidity of erythrocyte ghosts was measured by fluorescence technique and osmotic sensitivity of erythrocytes to the presence of TPhL. All parameters studied were found to be dependent on pH, of experimental solutions and the concentration of TPhL. Acidic conditions increased EC50, C100 and CC concentrations of TPhL. Fluorescence and osmotic measurements showed that osmotic stability and fluidity decreased with increasing trimethyllead concentration. A possible mechanism of TPhL toxicity is discussed. It is assumed that TPhL is interacting with the lipid phase of the models used. It is also assumed that there may exist various, ionic and nonionic, forms of TPhL as a result of its speciation under different experimental conditions. These species, due to their differentiated lipophilicity, may exert different effects on the model membranes studied.


1997 ◽  
Vol 52 (3-4) ◽  
pp. 209-216 ◽  
Author(s):  
Janina Gabrielska ◽  
Janusz Sarapuk ◽  
Stanisław Przestalski

AbstractThe present study was conducted to clarify the mechanism of toxicity of organic compounds using lipid model membranes (liposomes and planar lipid membranes).The compounds studied were trialkyltin and trialkyllead chlorides, dialkyltin dichlorides and some inorganic forms of those metals. Two different (anionic and cationic) detergents were also used in the experiments to change the surface properties of liposomes. As a measure of interaction between the compounds studied and model membranes were the release of liposome bound praseodymium and the change in stability of planar membranes under the influence of those compounds.On the basis of the results obtained it was postulated that the mechanism of interaction between tin-and leadorganics and model lipid membranes is a combination of different factors featuring interacting sides. The most important properties determining the behaviour of organic compounds in the interaction were lipophilicity and polarity of different parts of the organics and the steric arrangement they can take in the medium. On the other hand, the surface potential of the lipid bilayer and the environment of the lipid molecules, that play a significant role in the availability of the lipid bilayer to the organics, were important factors in the interaction.


Coatings ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 368 ◽  
Author(s):  
Katarzyna Karwowska ◽  
Ewelina Skrodzka ◽  
Joanna Kotyńska ◽  
Aneta D. Petelska

Interactions between components of model lipid membranes (spherical lipid bilayers and liposomes) are investigated here. Parameters characterizing equilibria in the 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)-diosgenin (Dio) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)-diosgenin acetate (DAc) membrane systems have been determined. The interfacial tension measurement of spherical lipid bilayers was based on the Young-Laplace’s equation using a homemade computer-controlled device. We assume a 1:1 complex in the DPPC-Dio and DPPC-DAc membrane systems. The parameters A 3 − 1 , the surface concentration of lipid membranes formed from these complexes, γ 3 , the interfacial tension of such membranes, and, K, the constant stability of these complexes were calculated. Microelectrophoresis was used for examinations of the surface charge density of lipid membranes. The values were obtained here from electrophoretic mobility data applying Smoluchowsky’s equation. The effect of pH (pH ranged of 2 to 10) on the electrolyte solution and the compositions of the membranes was analyzed. The obtained results indicate that the modification of DPPC membranes with both Dio and DAc causes changes in surface charge density values and shifts of the isoelectric point.


2020 ◽  
Vol 20 (16) ◽  
pp. 1966-1980
Author(s):  
Jaleh Varshosaz ◽  
Saeedeh Fardshouraki ◽  
Mina Mirian ◽  
Leila Safaeian ◽  
Setareh Jandaghian ◽  
...  

Background: Using imatinib, a tyrosine kinase inhibitor drug used in lymphoblastic leukemia, has always had limitations due to its cardiotoxicity and hepatotoxicity side effects. The objective of this study is to develop a target-oriented drug carrier to minimize these adverse effects by the controlled release of the drug. Methods: KIT-5 nanoparticles were functionalized with 3-aminopropyltriethoxysilane and conjugated to rituximab as the targeting agent for the CD20 positive receptors of the B-cells. Then they were loaded with imatinib and their physical properties were characterized. The cell cytotoxicity of the nanoparticles was studied by MTT assay in Ramos (CD20 positive) and Jurkat cell lines (CD20 negative) and their cellular uptake was shown by fluorescence microscope. Wistar rats received an intraperitoneal injection of 50 mg/kg of the free drug or targeted nanoparticles for 21 days. Then the level of aspartate Aminotransferase (AST), alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Lactate Dehydrogenase (LDH) were measured in serum of animals. The cardiotoxicity and hepatotoxicity of the drug were also studied by hematoxylin and eosin staining of the tissues. Results: The targeted nanoparticles of imatinib showed to be more cytotoxic to Ramos cells rather than Jurkat cells. The results of the biochemical analysis displayed a significant reduction in AST, ALT, ALP, and LDH levels in animals treated with targeted nanoparticles, compared to the free drug group. By comparison with the free imatinib, histopathological results represented less cardiotoxicity and hepatotoxicity in the animals, which received the drug through the current designed delivery system. Conclusion: The obtained results confirmed that the rituximab targeted KIT-5 nanoparticles are promising in the controlled release of imatinib and could decrease its cardiotoxicity and hepatotoxicity side effects.


2005 ◽  
Vol 70 (5) ◽  
pp. 668-675 ◽  
Author(s):  
Monika Hereć ◽  
Halina Dziubińska ◽  
Kazimierz Trębacz ◽  
Jacek W. Morzycki ◽  
Wiesław I. Gruszecki

2020 ◽  
Vol 15 (12) ◽  
pp. 1934578X2098210
Author(s):  
Nguyen Thi Nga ◽  
Do Thi Phuong ◽  
Nguyen Thi Cuc ◽  
Trieu Ha Phuong ◽  
Pham Thi Mai Huong ◽  
...  

Recently, saponins derived from marine sources have received much attention because of their promising bioactivities, such as anticancer, anti-angiogenesis, and anti-inflammation. In particular, a triterpene saponin from the sea cucumber Cercodemas anceps Selenka, cercodemasoide A (CAN1), showed potent cytotoxicity against various cancer cell lines. Recent evidence has indicated that cancer stem cells (CSCs) could be a novel target for efficient cancer therapies. In order to improve the biopharmaceutical properties of CAN1, the compound was loaded into nanoliposomes as an ideal drug carrier. CAN1 was successfully incorporated into nanoliposomes as small unilamellar liposome vesicles with an average size of 73.39 ± 1.57 nm, zeta potential of −0.299 ± 0.046 mV, polydispersity index of 0.336 ± 0.038, and with an encapsulation efficiency of up to 62.9%. For the first time, CAN1 and its nanoliposomal forms have been shown to have a promising cytotoxic activity against NTERA-2 CSCs, with half-maximal inhibitory concentration (IC50) =1.03 ± 0.04 and 0.41 ± 0.03 µM, respectively. The CAN1 nanoliposomes also presented significantly improved activities in suppressing the growth of NTERA-2 3-dimensional tumorspheres (IC50 = 1.71 ± 0.06 µM) in comparison with the free form ( P < .05). The anti-CSC effects of CAN1 nanoliposomes on NTERA-2 cells were due to their apoptotic induction through enhancing caspase-3 activity (more than 2-fold) and arresting the cell cycle at the S phase ( P < .05). The obtained CAN1-encapsulated nanoliposomes suggest valuable applications in CSC-targeting treatment for more efficient clinical therapy.


2013 ◽  
Vol 33 (5) ◽  
Author(s):  
Chi L. L. Pham ◽  
Roberto Cappai

The deposition of α-syn (α-synuclein) as amyloid fibrils and the selective loss of DA (dopamine) containing neurons in the substantia nigra are two key features of PD (Parkinson's disease). α-syn is a natively unfolded protein and adopts an α-helical conformation upon binding to lipid membrane. Oligomeric species of α-syn have been proposed to be the pathogenic species associated with PD because they can bind lipid membranes and disrupt membrane integrity. DA is readily oxidized to generate reactive intermediates and ROS (reactive oxygen species) and in the presence of DA, α-syn form of SDS-resistant soluble oligomers. It is postulated that the formation of the α-syn:DA oligomers involves the cross-linking of DA-melanin with α-syn, via covalent linkage, hydrogen and hydrophobic interactions. We investigate the effect of lipids on DA-induced α-syn oligomerization and studied the ability of α-syn:DA oligomers to interact with lipids vesicles. Our results show that the interaction of α-syn with lipids inhibits the formation of DA-induced α-syn oligomers. Moreover, the α-syn:DA oligomer cannot interact with lipid vesicles or cause membrane permeability. Thus, the formation of α-syn:DA oligomers may alter the actions of α-syn which require membrane association, leading to disruption of its normal cellular function.


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