Click Here

Walled Carbon Nanotubes With Model Lipid Membranes – Comparison Of The Interactions Of Daunorubicin In A Free Form And Attached To Single

pure water resistivity In order to compare the results for the two modified types electrodes in a more detailed way, surface concentration of the drug should be calculated.

It could be noted that the surface concentration of DNR calculated on the basis of electrochemical experiments is also identical for both mixed DPPTE SWCNTs DNR monolayer and incorporated drug in the free form.

While in the event of DNR attached to carbon nanotubes the content of DNR in the total percentage of the ‘DPPTESWCNTsDNR’ adduct administered at the airwater interface as a mixed layer and transferred onto the electrode was taken into account, in the event of daunorubicin in the free form the estimation was depending on the DNR concentration in the subphase and surface concentration of the drug incorporating into the model membrane precompressed to 30 mN/m. The estimated percentage of daunorubicin in the supported model membrane is equal to 4 × 10−13 and 1 × 10−13 mol for the free drug and drug attached to carbon nanotubes. Basing on the results of monolayer studies, the effect of SWCNTsDNR adducts on the properties of model DPPTE membranes is much smaller than the one observed for a free drug.

pure water resistivity

pure water resistivity It is especially important in the view of the application of carbon nanotubes as drug carriers.

It is interesting to compare the surface concentrations of the drug incorporated into the supported model membranes in the two forms.

This proves that the quantity of the drug in the model membrane is similar for both kinds of the types drug delivery. Our solution was to transfer the layer onto a solid substrate and evaluate the percentage of the drug present in the model membrane supported on the electrode by electrochemistry. Due to different solubilities, the experimental procedures are different. For instance, the initial concentrations of the drugs can not be easily compared. Supported DPPTE or mixed ‘DPPTESWCNTsDNR’ monolayers were prepared by means of Langmuir Blodgett method. The DPPTE and mixed ‘DPPTESWCNTsDNR’ layers were deposited on the gold surface by vertical withdrawal of the electrode at the speed of 25 mm/min to give a transfer ratio of 0 ± The target surface pressure, at which the layers were transferred was equal to 30 mN/m and 35 mN/m for DPPTE and mixed DPPTESWCNTsDNR monolayers. A well-known fact that is. Prior to the transfer, gold electrodes, that were 200 nm thick gold films evaporated onto borosilicate glass precoated with an underlayer of chromium, were flame annealed, cleaned in the mixture of H2O2/NH3/H2O with 5 ratio at 70 °C for approximately 5 min and thoroughly rinsed with ‘MilliQ’ water.

, since daunorubicin is electroactive and undergoes 2e−/2H+ redox process.

Such a significant increase is caused by the incorporation of DNR molecules into the thiolipid layer.

With intention to verify the presence of daunorubicin attached to carbon nanotubes in the mixed layer on the electrode, cyclic voltammetry was performed. It can be clearly observed that in the presence of daunorubicin in a free form in the subphase the shape of the isotherm changes significantly and the isotherm is shifted towards larger areas per molecule. The ‘reduction oxidation’ peaks observed in voltammograms correspond to the electrode process of the quinonehydroquinone group, that makes the direct comparison more difficult, some interesting and new insight into such interactions should be still provided. Now regarding the aforementioned fact… Significant changes concern the compression modulus and its maximum value. Considering the above said. Characteristic parameters describing the properties of the monolayer are also significantly changed, as observed in our previous studies concerning the influence of DNR on thiolipid model membranes. The area per molecule in a well organized monolayer increases from the value of 44 Å2 corresponding to the DPPTE monolayer formed on pure water subphase to the value of 74 Å2 in the presence of the drug in the subphase.

Supported layers were characterized by electrochemical techniques, after the B transfer described in detail in Experimental section. Additionally, the shape of the isotherms is altered and the broad plateau region corresponding to the phase transition is clearly visible at relatively high surface pressure of 38 mN/m, since the molar percentage of the DNR in the adduct is equal only to 15percentage. Of course, different situation occurs when daunorubicin attached to carbon nanotubes is introduced into DPPTE monolayers. Considering the above said. Undoubtedly it’s still in the range corresponding to the solid phase, its value decreases to 325 mN/m, that is 70 mN/m less than the value reported for pure DPPTE monolayer.

In case of mixed DPPTE SWCNTs DNR layer the isotherms are only slightly altered.

It going to be also noted that for quite similar weight ratio of the components there’s no significant difference between the effect of the unmodified CNTs and CNTs drug adducts in the mixed layer.

Interestingly, the presence of small percentage of SWCNTs leads to the increase in the maximum value of compression modulus compared to DPPTE monolayers formed on water subphase. Accordingly the isotherm shape isn’t significantly changed, when the percentage of drug carrier is relativelyquite small compared to the prevailing percentage of the lipid. Make sure you scratch a comment about it below. The presence of bigger amounts of carbon nanotubes in the mixed layers, more pronounced changes are observed if of the compression modulus. The isotherms obtained for mixed layers containing DPPTE and carbon nanotubes with and without drug are almost identical. That is interesting. Other characteristic parameters similar to collapse area and collapse pressure do not change greatly, this place per molecule increases by a few angstroms from the value of 44 Å2 corresponding to the DPPTE monolayer formed on pure water subphase to the value of 49 Å2.

Langmuir monolayers were prepared using a KSV LB trough 5000 equipped with hydrophilic barriers and a Wilhelmy balance made from a filter paper used as a surface pressure sensor.

The detailed procedure of the covalent end modification of singlewalled carbon nanotubes with daunorubicin by the formation of hydrazone was inspired by the protocol previously described for side and end carboxylated SWCNTs modification.

The modification at the ends of the nanotubes as well as in the defect sites was obtained by the formation of ‘SWCNTs end’ hydrazide, that was therefore mixed with daunorubicin to form hydrazone. Generally, the experiment was controlled with software version KSV ’12dipalmitoylsnglycero3phosphothioethanol’ was dissolved in chloroform to give 1 mg/mL stock solution. Prior to the deposition at the air water interface, the mixed solutions were sonicated in the ultrasonic bath for approximately 30 min to ensure carbon nanotubes dispersion. Nevertheless, langmuir monolayers were prepared on either ‘Milli Q’ ultra pure water subphase or subphase containing daunorubicin. Carbon nanotubes used for the modification were commercial, oxidized nanotubes ‘SWCNTCOOH’ with the diameter of 1 2 nm and length of ‘5 30’ µm. However, barrier speed during compression was 10 mm/min. Basing on the TGA analysis such modification procedure yields the functionalization degree in the order of approximately 25 × 10−7 drug mol per 1 mg of carbon nanotubes.

pure water resistivity

Mixed DPPTE SWCNTs DNR dispersion was prepared by weighing approximately 5 modified mg nanotubes and adding the appropriate volume of DPPTE stock solution to obtain the desired weight ratio of carbon nanotubes to thiolipid. Few drops of the solution after careful cleaning of the subphase. The drug was either in the free form dissolved in the subphase, on which the DPPTE monolayer was formed, or attached to single walled carbon nanotubes, that are potential drug carriers. Notice that the organization of the monolayer ain’t influenced to this particular large extent and even at the higher weigh content of CNTs in the mixed layer, the monolayer retains its solid character. The characteristic parameters just like area per molecule do not change as significantly as if of a free drug. I’m sure you heard about this. Interactions of anticancer drug daunorubicin with model thiolipid membranes were investigated using Langmuir technique and electrochemical methods.

Results of the studies with ‘SWCNTsDNR’ conjugates revealed that their influence on DPPTE monolayers is much less pronounced.

The observed differences in the properties of the monolayer are caused by the electrostatic interactions between the positively charged drugs and negatively charged polar heads of the lipid.

Langmuir studies revealed that DNR influences the properties of the thiolipid monolayer leading to a significant increase in this place per molecule. In this case, drug carrier adducts were deposited onto the airwater interface forming the mixed layers of DPPTE with differing weight ratio of the components. Of course additionally, the organization of the monolayer changes. Basically the mixed layers composed of DPPTE and ‘SWCNTs DNR’ adduct were prepared with either prevailing weight ratio of nanotubes or prevailing weight ratio of thiolipid. It is drug in a free form was dissolved in the subphase, on which monolayers of DPPTE were formed. You should take it into account. In order to study the influence of daunorubicin in a free form and attached to carbon nanotubes as potential drug carrier, Langmuir technique was employed.

It was impossible to dissolve the carbon nanotube adducts in the subphase as long as their insufficient solubility in water, if of DNR attached to carbon nanotubes.

There are different mechanisms proposed to explain the cellular uptake of CNTs including the passive diffusion in a noninvasive manner.

The observed changes in the DPPTE monolayer behavior in the presence of both free drug and drug attached to carbon nanotubes may be explained regarding the different driving forces responsible for the interactions. On top of in the significant increase in this place per molecule in the organized layer are among the promising drug delivery systems, those kinds of interactions types result both in the observed changes in the Cs−1 values. It strongly depends on the dimensions and functionalization type, that may significantly increase their biocompatibility, even if toxicity of the nanotubes is a big poser. With the increasing surface pressure DNR molecules may penetrate deeper into the monolayer and after that hydrophobic interactions also play important role. Changes in the properties of DPPTE membrane were attributed to the electrostatic interactions.

When the drug dissolved in the subphase first interacts with polar heads of the lipid, electrostatic interactions is likely to be playing the most important role, especially if of the interactions at lower surface pressures, Obviously, hydrophobic interactions between the hydrophobic part of the drug and acyl chains of the lipids might be also taken into account.

Carbon nanotubes are successfully used to transport different kinds of anticancer types agents including camptothecin, doxorubicin and daunorubicin.

In those works daunorubicin was conjugated to either polyethylene glycol functionalized ‘single walled’ carbon nanotubes or to ‘aptamerwrapped’ SWCNTs via π π interactions. At the pH corresponding to pure water So there’s electrostatic attraction between the negatively charged polar heads of the lipid and positively charged drug, since the thiolipid molecules are negatively charged and pKa of daunorubicin is equal to 4. The two main methods of attaching the drugs comprise either covalent attachment or physical adsorption on the basis of π π stacking interactions. They attract scientists’ attention since their properties just like stability, robustness, high drug carrying capacity and ability to penetrate cell membranes. Such significant changes in the isotherm shape and dramatic decrease in the maximum value of compression modulus implies that upon the incorporation into DPPTE monolayer, DNR disorganizes the thiolipid monolayer and causes its fluidization, if of free daunorubicin interactions.

There are a few reports in the literature on the preparation and characterization of CNTsDNR adducts used as drug delivery systems.

In the next step, voltammograms obtained after the incubation in DNR solution were compared with the voltammograms recorded for electrodes modified with DPPTE monolayer and electrodes modified with mixed DPPTE SWCNTs DNR monolayers.

No reduction oxidation peaks can be observed, the control experiments on the effect of unmodified SWCNTs in the supported layers are not shown as in the absence of electroactive species similar to daunorubicin attached to carbon nanotubes on the electrode surface nor thiolipid undergo ‘reduction oxidation’ processes in the potential range investigated. In case of both DPPTE monolayers exposed to DNR solution and mixed DPPTE SWCNTs DNR monolayers the ‘oxidation reduction’ peaks corresponding to the electrode process of daunorubicin are observed and the peak currents are similar. For example, this thiolipid had been used so far either as a tethering layer in tBLM systems employed, for studying ionchannel proteins on electrode surfaces or as a model membrane in the studies of a lipolytic enzyme, phospholipase A2, that was employed as a tool for modifying the structure of supported thiolipid layers in a controlled way.

pure water resistivity

Due to the presence of a thiol group in the polar headgroup region, that said, this lipid has negative charge and it’s possible to transfer monolayers onto solid support by means of both Langmuir Blodgett method and selfassembly, that results in the differences in the packing of the thiolipid molecules in the supported layers relying on the mode of transfer.

Our previous results of Langmuir studies show that daunorubicin in a free form may easily incorporate into the DPPTE layers during their formation and significantly change the properties of the layers.

The effect of daunorubicin attached to carbon nanotubes as potential drug carrier on the properties of model membranes is compared to that reported for a free drug. In this study the influence of both free daunorubicin and daunorubicin attached via covalent bond to ‘singlewalled’ carbon nanotubes. Nevertheless, electrochemical experiments were performed using AutoLab AUT 71819 with the GPES 9 software in the three electrode system with Ag/AgCl as a reference electrode and platinum foil as a counter electrode.

pure water resistivity

In order to assess the interactions of the free daunorubicin with model membranes, DPPTE monolayers were transferred by means of LB method onto gold electrodes and were exposed to 10−5 M DNR solutions for 600 s to ensure the incorporation of the drug into the model membrane.

Additionally, it corresponds to the concentrations used in the in vitro studies.

Alternatively, That’s a fact, it’s also possible to incorporate the drug into the model membrane during its formation and later transfer it onto the electrode. It could be also stressed that the concentration used for the incubation of the modified electrodes is consistent with the DNR concentration used in monolayer studies. Basically, the optimal incubation time of the model membrane in the drug solution was depending on our previous studies, that showed that after this time cyclic voltammograms become stable. It is 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.

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 if of the incorporation of a free drug, that resulted in a significant increase in the position per molecule and fluidization of the thiolipid layer.

The presence of SWCNTsDNR in the DPPTE monolayer at the ‘airwater’ interface did not change the organization of the lipid molecules to such extent as the free drug, that may be explained by different kinds of interactions types playing crucial role in these two systems types.

While in the case of ‘SWCNTs DNR’ adducts the hydrophobic interactions between nanotubes and acyl chains of the lipid is prevailing, 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.

The results obtained for a free drug were compared with the results recorded for DNR attached to SWCNTs as potential drug carrier. In this work the interactions of an anticancer drug daunorubicin with model thiolipid layers composed of ’12 dipalmitoyl sn glycero 3 phosphothioethanol’ were investigated using Langmuir technique. Such magnetic nanoparticles conjugated with DNR were reported to induce apoptosis of cancer cell lines. Magnetic Fe3O4 nanoparticles are often employed since they give possibility to control the transport by applying external magnetic fields. Did you hear about something like that before? Drug delivery systems are aimed at providing enhanced transport of therapeutic agents directly to the targeted organs and tissues, that enables the elimination or significant decrease in the consequences of a drug.

The most common drug type nanocarriers includes liposomes, that are commercially available daunorubicin formulation used in the treatment of Kaposi’s sarcoma.

Another common type drug carriers includes nanoparticles.

Dual drug loading is also employed in the event of other DDS like biodegradable polymers, that co assemble into composite micelles. Other examples of nanoparticles include titanium dioxide. Despite that, there’re still numerous studies on the improvement of this drug delivery system aiming at enhancing drug loading into cells by using specific interactions between targeting agents and their receptors, just like as an example folates and transferrin. Additionally, liposomes are also prepared in this type of a way that simultaneous loading of two drugs into a liposome with intention to improve the efficiency of the treatment is possible. It was shown that the surface concentration of the drug on the electrode surface is similar for both the drug in a free form and the drug nanocarrier adduct. Besides, cyclic voltammetry performed for the electrodes modified with DPPTE monolayers containing daunorubicin either in the free form or attached to carbon nanotubes proved the presence of the electroactive drug at the electrode surface.

pure water resistivity

Electrochemistry was also employed to compare the model membranes containing daunorubicin in the two investigated forms. This observation proves that application of singlewalled carbon nanotubes as drug delivery system allows for the transport of the comparable percentage of the drug with respect to the drug in a free form but the influence of the drugcarrier adduct on the model membranes is much smaller. They should be also squeezed out from the monolayer into the subphase or into the close vicinity of the monolayer. Normally, the increasing quantity of the nanotubes in the mixed layer results in some fluidization of the DPPTE monolayer as long as the increasing number of nanotubes prevents from the hydrophobic interactions between acyl chains of the lipid and thus leads to the disorganization of the layer.

Additionally, the relativelyvery small increase in this location per molecule with the increasing content of the nanotubes in the thiolipid monolayer (from 48 dot 6 to 50 dot 4 Å2 for the prevailing weight ratio of the lipid and the nanotubes, respectively, Tableindicates that the nanotubes may form aggregates or bundles and do not distribute evenly within the thiolipid monolayer.

In the presence of SWCNTs DNR conjugates the isotherms are only slightly shifted towards larger areas per molecule but their shape ain’t altered.

In identical time, the nanotubes occupy the interfacial area and therefore a small increase in the position per molecule is observed. Alternatively, closing the barriers and increasing the surface pressure may lead to the foregoing mentioned formation of aggregates or bundles. The unexpected increase in the maximum value of compression modulus for the mixed layers with the prevailing quantity of thiolipid should be caused by the fact that since the presence of relativelyquite small amounts of carbon nanotubes in the monolayer the thiolipid molecules become more oriented with less tilted hydrocarbon chains, that leads to the observed increase in the maximum value of compression modulus. In case of the effect of SWCNTs modified with DNR different explanation can be given.

pure water resistivity

With that said, this influence isn’t as significant as the influence of DNR in the free form and therefore it does not introduce the change of the phase of the monolayer. Similar observation was made by Cancino et al, who studied the effect of carbon nanotubesdendrimers nanoconjugates on DPPC monolayers.

Leave a comment

Your email address will not be published.