Interaction Of Drug Molecules Research Articles

Exploring the binding interaction of Bis-benzimidazoles with BSA and relocation of bound drug from BSA to DNA

In recent years Bis-benzimidazole derivatives have gained much research interest due to their regulatory role in biological reactions to control diseases. Therefore, probing the interaction of the bioactive derivatives with biomolecules is crucial for both physiological and pharmacological aspects. Consequently, we studied the interaction between Bis-benzimidazoles and bovine serum albumin (BSA) as model transport protein by multi-spectroscopic techniques. It was also evident that substitutions of the phenolic OH group of Hoechst-33258 by -OMe and -NEt2 group have negligible impact on the binding phenomenon with BSA. Additionally, we have shown that the bound derivatives can be successfully relocated from serum albumin to calf-thymus DNA (ct-DNA). The observed higher binding affinity of the Hoechst-33258 to ct-DNA than BSA was responsible for the relocation of dyes from BSA to DNA. The competitive displacement assay with known site markers revealed that the probable binding location of the Hoechst-33258 within the serum protein was site IB. Molecular docking study was also performed to support the experimental findings and to obtain the possible interaction of drug molecule in the protein environment. Our findings might be helpful in overcoming the challenges associated with the delivery of bis-benzimidazole derivatives.

Electrochemical Studies on Interaction of Ofloxacin with ITO-PANI Supported Bilayer Lipid Membrane

Bilayer phospholipid membrane was formed on the ITO-Pani surface in NaCl bath solution at different pH. Characterization and interaction of bilayer lipid membrane (BLM) with Ofloxacin molecules in 0.1 M NaCl solution was studied at different pH employing electrochemical impedance spectroscopy, cyclic voltammetry and chronoamperometric methods. The changes in the properties of BLM due to addition of Ofloxacin depends on the pH of bath solution. At low pH the membrane surface is positively charged and the interaction of drug molecules with the BLM surface takes place through chloride bridge. At alkaline pH the membrane surface is negatively charged and the drug molecules get attached through hydrogen bonding. The results of electrochemical impedance spectroscopy, cyclic voltammetry and chronoamperometry support each other.

Binding of dicoumarol analog with DNA and its antioxidant studies: A biophysical insight by in-vitro and in-silico approaches

DNA is the major target for a number of pharmaceutical drugs. The interaction of drug molecules with DNA plays a major role in pharmacokinetics and pharmacodynamics. Bis-coumarin derivatives have diverse biological properties. Here, we have explored the antioxidant activity of 3,3′-Carbonylbis (7-diethylamino coumarin) (CDC) using DPPH, H2O2, and superoxide scavenging studies followed by its binding mode in calf thymus-DNA (CT-DNA) using several biophysical methods including molecular docking. CDC exhibited comparable antioxidant activity to standard ascorbic acid. The UV–Visible and fluorescence spectral variations indicate the CDC-DNA complex formation. The binding constant in the range of 104 M−1 was obtained from spectroscopic studies at room temperature. The fluorescence quenching of CDC by CT-DNA suggested a quenching constant (KSV) of 103 to 104 M−1 order. Thermodynamic studies at 303, 308, and 318 K revealed the observed quenching as a dynamic process besides the spontaneity of the interaction with negative free energy change. Competitive binding studies with site markers like ethidium bromide, methylene blue, and Hoechst 33258 reflect CDC's groove mode of interaction. The result was complemented by DNA melting study, viscosity measurement, and KI quenching studies. The ionic strength effect was studied to interpret the electrostatic interaction and found its insignificant role in the binding. Molecular docking studies suggested the binding location of CDC within the minor groove of CT-DNA, complementing the experimental result.

DFT-based theoretical model for predicting the loading and release of pH-responsive paracetamol drug

Here, we provide a theoretical framework that integrates quantum mechanical calculations with classical pKa theory to forecast the degree of interaction of drug molecules with carrier surfaces across the whole pH range. The drug loading and release of a pH-responsive drug delivery system is demonstrated using paracetamol drug carried using mesoporous silica surface with and without trimethylammonium (TA) functional group. The model is explained on the basis of possible combinations of surface (S) and drug (D) molecules as neutral (0) and deprotonated (1) pH-dependent states. The relative probabilities of these states depend on the pKa values of the drug as well as surface and the desired pH. Paracetamol, an analgesic and antipyretic drug, is required to be absorbed in small intestine and not in the stomach. It’s seen that Paracetamol is caught in the MSN-TA nano-vehicle when it goes throughthe acidic environment of the stomach and then released in the slightly basic pH of the intestine. The reported model from the literature is used for forecasting the loading and release pH for the Paracetamol using mesoporous silica surface.

An overview of theoretical investigations on interaction of drug molecule with functionalized carbon nanotubes as drug delivery system

CNTs are promising nano-carriers for both drugs as well as biomolecules. This study possesses in-depth knowledge and understanding of carbon nanotubes both for their pharmaco-toxicological properties in drug molecule, it is essential to recommended for routine clinical use in the form of drug delivery carriers in the diagnosis and treatments of many diseases. The surface modified or functionalized Carbon nanotubes (CNTs) can be used for different purposes like improving solubility, carrying various therapeutic, and targeting agents. The functionalization of CNTs can be done via covalent or noncovalent bonding. The Density functional theory calculations are very much helpful to understand the effects on covalently binding of drug molecule with functionalized carbon nanotubes and fullerenes. The present review focus on the structural stability of drug molecule and adsorption behaviour of molecules over various types of CNTs. In addition, progress in carbon nanotube technology may well lead to better insights into biological and physical chemistry processes through theoretical calculations. This will make it possible to find drug molecules more compatible with carbon nanotube to facilitate in medical field.

How does aggregation of doxorubicin molecules affect its solvation and membrane penetration?

Aggregation and dynamics of Doxorubicin in solvents like water, DMF, EtOH, DMSO and at DPPC/water and octanol/water interfaces were studied using molecular dynamics (MD) simulations.

Pathology of drug hypersensitivity reactions and mechanisms of immune tolerance.

Immune-mediated type IV adverse drug reactions are idiosyncratic in nature, generally not related to the primary or secondary pharmacology of the drug. Due to their complex nature and rarity, these iatrogenic reactions are seldom predicted or encountered during preclinical/early clinical development stages, and often precipitate upon exposure to wider populations (i.e. phase III onwards). They confer a burden on the healthcare sector in both a clinical and financial sense presenting a severe impediment to the drug discovery and development process. Research over the past 50 years has improved our understanding of these reactions markedly as both in vitro and in vivo studies have placed the role of the immune system, in particular; drug-responsive T cells, firmly in the spotlight as the mediators of these reactions. Indeed, the role of different populations of T cells in adverse events and the interaction of drug molecules with HLA proteins expressed on the surface of antigen-presenting cells is of considerable interest. Herein, this review examines the pathways of immune-mediated adverse events including the various T cell subtypes implicated and the mechanisms of T cell activation. Additionally, we address the enigma of immunological tolerance and explore the role tolerance plays in determination of susceptibility to such adverse events even in individuals carrying immunogenic liabilities.

Understanding delivery and adsorption of Flutamide drug with ZnONS based on: Dispersion-corrected DFT calculations and MD simulations

The unique features of zinc oxide nanosheet (ZnONS) as an appropriate platform for Flutamide molecule was considered by means of density functional theory (DFT) framework with van der Waals (vdW) approximation via Perdew–Burke–Ernzerhof variant of the generalized gradient approximation (PBE-GGA) method along with double zeta polarization (DZP) basis set. The most stable model of interaction between Flutamide molecule and ZnONS is specified and adsorption energies (Eads) are assessed. In energetically favorable configuration, O atoms of –NO2 group of Flutamide interacts with a Zn atom of the ZnONS at 2.11 Å with Eads of −20.616 kcal mol−1. We have scrutinized charge analysis between species involved through famous Mulliken, Hirshfeld and Voronoi approaches. Furthermore, we have examined the density of states (DOS) and the projected density of states (PDOS) for the energetically favorable model to explore the interaction of the drug molecule with the ZnONS. Besides, quantum molecular descriptors (QMD) are also analyzed upon interaction of drug molecule on ZnONS. To deeper knowledge the details of the interaction between the Flutamide and the ZnONS, Quantum Theory of Atoms in Molecules (QTAIM) calculations are implemented. The values of ▽2ρ(BCP) and H(BCP) for (Flutamide)O⋯Zn(ZnONS) at the most stable configuration are positive and G/|V| is greater than 1, it denotes the non-covalent interaction between Flutamide with ZnONS. The DFT calculation based on molecular dynamics (MD) approach are utilized to acquire a better understand into the nature of the Flutamide drug and ZnONS interactions. The MD outcomes demonstrate that when the Flutamide molecule takes longer time to link with ZnONS, the Flutamide/ZnONS complex becomes stable. Moreover, after Flutamide molecule adsorption phenomenon the electrical conductivity generates an electrical signal. The outcomes affirmed the potential of a ZnONS as a drug delivery system (DDS) for drug molecule to remedy cancer and may be an appropriate sensor for the Flutamide drug detection.

CellSys: An open-source tool for building initial structures for bio-membranes and drug-delivery systems.

Since phospholipids are the most important components in the structure of biomembranes, they deserve to be considered with a lot of attention in both experimental and computational theoretical studies using molecular simulation methods related to the research in the fields of drug design and drug delivery where they involve knowledge about the interactions of drug molecules with cell membranes. To employ the molecular simulation approach for this purpose the essential requirement is having information about the initial structure of phospholipids and how they interact with the drugs. Therefore in this article, we introduce an open-source software package in Python programming language for utilizing data manipulation for generation and developing the initial structure of biomolecular cells to provide the needed information for investigation in drug delivery systems. In addition, the proposed software package can be used for the efficient storage of membrane structural data to be exploited in designing new drug delivery systems. To verify the performance of the code and the results of the simulations, several analyses have been done, such as the calculation of area per lipid and self-diffusion coefficient, in addition to lipid order parameter. The results were in complete agreement with the references.

Plant Derived Bioactive Compounds, Their Anti-Cancer Effects and In Silico Approaches as an Alternative Target Treatment Strategy for Breast Cancer: An Updated Overview.

Simple SummaryBreast cancer is one of the leading causes of death among women worldwide. Breast cancer may be provoked due to several physical, chemical and environmental factors. Moreover, genetic alternations that are inherited via generations may be a reason for the occurrence of cancer. When the cancer is benign, several therapeutic approaches are available to treat it. In case of malignancy, cancer may spread to other body parts and lead to death. Recent studies focus on the use of indigenous medicinal plants for the treatment of various cancers and particularly breast cancer. This could be an alternative to other treatment methods, as they cause minimal side effects when compared to chemo-drugs. In addition to that, high-throughput omics tools have paved the way for efficient drug targeting, and it would be a promising application for finding the interaction of drug molecules in human systems.Cancer is one of the most common malignant diseases that occur worldwide, among which breast cancer is the second leading cause of death in women. The subtypes are associated with differences in the outcome and were selected for treatments according to the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor. Triple-negative breast cancer, one of the subtypes of breast cancer, is difficult to treat and can even lead to death. If breast cancer is not treated during the initial stages, it may spread to nearby organs, a process called metastasis, through the blood or lymph system. For in vitro studies, MCF-7, MDA-MB-231, MDA-MB-468, and T47B are the most commonly used breast cancer cell lines. Clinically, chemotherapy and radiotherapy are usually expensive and can also cause side effects. To overcome these issues, medicinal plants could be the best alternative for chemotherapeutic drugs with fewer side effects and cost-effectiveness. Furthermore, the genes involved in breast cancer can be regulated and synergized with signaling molecules to suppress the proliferation of breast cancer cells. In addition, nanoparticles encapsulating (nano-encapsulation) medicinal plant extracts showed a significant reduction in the apoptotic and cytotoxic activities of breast cancer cells. This present review mainly speculates an overview of the native medicinal plant derived anti-cancerous compounds with its efficiency, types and pathways involved in breast cancer along with its genes, the mechanism of breast cancer brain metastasis, chemoresistivity and its mechanism, bioinformatics approaches which could be an effective alternative for drug discovery.

First-principles study of the binding affinity of monolayer BC6N nanosheet: Implications for drug delivery

The adsorption properties and most possible interactions of hydroxyurea (HU), 5-fluorouracil (5-FU), carmustine (CMU), 6-mercaptopurine (6-MP), ifosfamide (IFO), and chloromethane (CM) anticancer drug molecules with g-BC6N nanosheet were explored using density functional theory (DFT) in both gas and water solution at B3PW91/6-31G(d,p) level of theory. The various orientations for the interaction of drug molecules with the g-BC6N nanosheet revealed that adsorption energy values were strengthened and favored when drug molecules interact with the boron atom (B73) on the edge side of the g-BC6N nanosheet through their oxygen or nitrogen atoms. The most stable structure was observed for the 6-MP/g-BC6N complex with the adsorption energies of −18.19 and −23.53 kcal mol−1 for configurations M1 and M2 in the gas phase, respectively. The values of adsorption energies showed a slight increase in the stability of drug/g-BC6N complexes by the inclusion of water solution as a preferred environment for drug delivery systems. Quantum theory of atoms in molecules (QTAIM) analysis revealed the presence of electrostatic with partially covalent interactions in all complexes. Frontier molecular orbital analysis (FMO) showed that the energy band gap (Eg) of g-BC6N nanosheet is significantly reduced after drug adsorption. Furthermore, UV–Vis absorption spectrum analysis revealed a redshift for HU/g-BC6N, 5-FU/g-BC6N, CMU/g-BC6N, and 6-MP/g-BC6N complexes, while a blueshift was observed for CM/g-BC6N complex. Finally, physisorption of drug molecule by g-BC6N nanosheet leads to a lower recovery time and higher facility of drug release for all systems, which is suitable for drug delivery applications.

Specific and nonspecific binding of drug eluted from a half-embedded stent in presence of atherosclerotic plaque

This study is dealt with the two-phase binding (specific and nonspecific) of drug eluted from a half- embedded drug-eluting stent in presence of atherosclerotic plaque. The specific binding due to the interaction of drug molecules with specific receptors and nonspecific binding caused by the trapping of drug in the extra-cellular matrix have been paid due attention. An idealised wall consisting of a plaque and a healthy tissue region has been considered. Moreover, a Dirichlet release condition is imposed on the strut surface. In this investigation, a two-dimensional model governing drug transport and its two-phase binding in cylindrical polar coordinate system has been solved numerically by a finite-difference method. Our simulation predicts that plaque behaves like a physical barrier in two types of the binding process and there is an inverse relationship between bound drug concentration and plaque thickness. Simulations show that a single peak profile of drug is noted when the struts are situated one-strut radius apart and as the inter-strut distance increases, the peak concentration falls and distinct peak profiles over each strut are visualised. The model also reveals that in the region downstream of a strut, the concentration of both bound drug forms in the plaque and healthy regions increases, and eventually, the saturation length of binding sites increases. Predicted results show for smaller Damköhler number, the rapid saturation of binding sites takes place and the stent having thinner strut may perform well in terms of effectiveness as well as efficacy in the stent-based delivery.

Exploring the Nucleobase-Specific Hydrophobic Interaction of Cryptolepine Hydrate with RNA and Its Subsequent Sequestration.

The study of the interactions of drug molecules with genetic materials plays a key role underlying the development of new drugs for many life-threatening diseases in pharmaceutical industries. Understanding their fundamental base-specific and/or groove-binding interaction is crucial to target the genetic material with an external drug, which can pave the way to curing diseases related to the genetic material. Here, we studied the interaction of cryptolepine hydrate (CRYP) with RNA under physiological conditions knowing the antimalarial and anticancer activities of the drug. Our experiments explicitly demonstrate that CRYP interacts with the guanine- and adenine-rich region within the RNA duplex. The pivotal role of the hydrophobic interaction governing the interaction is substantiated by temperature-dependent isothermal titration calorimetry experiments and spectroscopic studies. Circular dichroism study underpins a principally intercalative mode of binding of CRYP with RNA. This interaction is found to be drastically affected in the presence of magnesium salt, which has a strong propensity to coordinate with RNA nucleobases, which can in turn modulate the interaction of the drug with RNA. The temperature-dependent calorimetric results substantiate the occurrence of entropy-enthalpy compensation, which enabled us to rule out the possibility of groove binding of the drug with RNA. Furthermore, our results also show the application of host-guest chemistry in sequestering the RNA-bound drug, which is crucial to the development of safer therapeutic applications.

Novel inexpensive ‘turn-on’ fluorescent biosensor for the sensitive detection of DNA damage induced by epirubicin

For several decades, DNA has been well-known as the cellular target for various cytotoxic anticancer drugs. An active research area between chemistry, medicine and molecular biology is studying mechanism of interaction of drug molecules with DNA. In this study, we introduce a novel inexpensive and simple fluorescent biosensor to directly quantitate the DNA damage induced by epirubicin, an anticancer agent, and investigate the underlying molecular mechanisms of damage. The proposed fluorescent biosensor is established using terbium chloride. In damaged DNA, there are ssDNA regions facing the damaged nucleobases. In the damaged DNA, the terbium biosensor coordinates directly with the unpaired nucleobases accompanied by enhancement of its fluorescence, generating a measureable signal proportionate to the amount of damage. Moreover, dithiothreitol is used in this study to asses any possible DNA damage mechanisms that may occur other than the DNA oxidative damage that is commonly induced by various anthracyclines. In this work, the kinetics of the damage induced in DNA by epirubicin in absence and presence of dithiothreitol were compared using the proposed Tb3+ fluorescence biosensor. The results were confirmed using MALDI-TOF mass spectrometric analysis. It revealed that in absence of dithiothreitol, epirubicin induces oxidative DNA damage due to the interaction with reactive oxygen species causing strand breaks where the mass spectra show a significant reduction of the molecular-ion-peak of DNA, and appearance of peaks of smaller m/z indicating the DNA strand-breaks formation. While, in presence of dithiothreitol, epirubicin covalently binds to DNA to form DNA adducts with m/z values larger than the molecular-ion-peak of DNA target. Furthermore, the potency of epirubicin was examined on calf-thymus natural DNA samples with the proposed fluorescence biosensor. Whilst the interaction mechanism of epirubicin with DNA in presence of dithiothreitol shows slower DNA damage kinetics, but it has more potent damaging effect on DNA than in the case when no dithiothreitol is added. This introduces a novel alternative anticancer therapy that requires further investigation. Moreover, the low cost of the proposed fluorescent biosensor allows it to be an automatic simple process for the investigation of any DNA-drug interactions without the need to couple it with any other analytical method.

Alterations in the HLA-B*57:01 Immunopeptidome by Flucloxacillin and Immunogenicity of Drug-Haptenated Peptides.

Neoantigen formation due to the interaction of drug molecules with human leukocyte antigen (HLA)-peptide complexes can lead to severe hypersensitivity reactions. Flucloxacillin (FLX), a β-lactam antibiotic for narrow-spectrum gram-positive bacterial infections, has been associated with severe immune-mediated drug-induced liver injury caused by an influx of T-lymphocytes targeting liver cells potentially recognizing drug-haptenated peptides in the context of HLA-B*57:01. To identify immunopeptidome changes that could lead to drug-driven immunogenicity, we used mass spectrometry to characterize the proteome and immunopeptidome of B-lymphoblastoid cells solely expressing HLA-B*57:01 as MHC-I molecules. Selected drug-conjugated peptides identified in these cells were synthesized and tested for their immunogenicity in HLA-B*57:01-transgenic mice. T cell responses were evaluated in vitro by immune assays. The immunopeptidome of FLX-treated cells was more diverse than that of untreated cells, enriched with peptides containing carboxy-terminal tryptophan and FLX-haptenated lysine residues on peptides. Selected FLX-modified peptides with drug on P4 and P6 induced drug-specific CD8+ T cells in vivo. FLX was also found directly linked to the HLA K146 that could interfere with KIR-3DL or peptide interactions. These studies identify a novel effect of antibiotics to alter anchor residue frequencies in HLA-presented peptides which may impact drug-induced inflammation. Covalent FLX-modified lysines on peptides mapped drug-specific immunogenicity primarily at P4 and P6 suggesting these peptide sites as drivers of off-target adverse reactions mediated by FLX. FLX modifications on HLA-B*57:01-exposed lysines may also impact interactions with KIR or TCR and subsequent NK and T cell function.

Differential Scanning Calorimetry (DSC) on Sartan/Cyclodextrin Delivery Formulations.

Differential scanning calorimetry (DSC) is a widely utilized method for the interactions of drug molecules with drug delivery systems (DDSs). Herein is described a protocol for studying the interactions and entrapment efficiency of the prototype sartan losartan and the polydynamic, structurally similar irbesartan inside the nontoxic 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD). The thermal scan properties of both sartan molecules have been studied when physically mixed or complexed with the cyclodextrin. The thermograms indeed showed significant differences between the mixtures and complexes, establishing DSC as a valuable method to characterize the state of the drugs in these pharmaceutical formulations.

In silico molecular target prediction unveils mebendazole as a potent MAPK14 inhibitor.

The concept of polypharmacology involves the interaction of drug molecules with multiple molecular targets. It provides a unique opportunity for the repurposing of already-approved drugs to target key factors involved in human diseases. Herein, we used an insilico target prediction algorithm to investigate the mechanism of action of mebendazole, an antihelminthic drug, currently repurposed in the treatment of brain tumors. First, we confirmed that mebendazole decreased the viability of glioblastoma cells invitro (IC50 values ranging from 288nm to 2.1µm). Our insilico approach unveiled 21 putative molecular targets for mebendazole, including 12 proteins significantly upregulated at the gene level in glioblastoma as compared to normal brain tissue (fold change >1.5; P<0.0001). Validation experiments were performed on three major kinases involved in cancer biology: ABL1, MAPK1/ERK2, and MAPK14/p38α. Mebendazole could inhibit the activity of these kinases invitro in a dose-dependent manner, with a high potency against MAPK14 (IC50 =104±46nm). Its direct binding to MAPK14 was further validated invitro, and inhibition of MAPK14 kinase activity was confirmed in live glioblastoma cells. Consistent with biophysical data, molecular modeling suggested that mebendazole was able to bind to the catalytic site of MAPK14. Finally, gene silencing demonstrated that MAPK14 is involved in glioblastoma tumor spheroid growth and response to mebendazole treatment. This study thus highlighted the role of MAPK14 in the anticancer mechanism of action of mebendazole and provides further rationale for the pharmacological targeting of MAPK14 in brain tumors. It also opens new avenues for the development of novel MAPK14/p38α inhibitors to treat human diseases.

Membrane Interaction of Ibuprofen with Cholesterol-Containing Lipid Membranes.

Deciphering the membrane interaction of drug molecules is important for improving drug delivery, cellular uptake, and the understanding of side effects of a given drug molecule. For the anti-inflammatory drug ibuprofen, several studies reported contradictory results regarding the impact of ibuprofen on cholesterol-containing lipid membranes. Here, we investigated membrane localization and orientation as well as the influence of ibuprofen on membrane properties in POPC/cholesterol bilayers using solid-state NMR spectroscopy and other biophysical assays. The presence of ibuprofen disturbs the molecular order of phospholipids as shown by alterations of the 2H and 31P-NMR spectra of the lipids, but does not lead to an increased membrane permeability or changes of the phase state of the bilayer. 1H MAS NOESY NMR results demonstrate that ibuprofen adopts a mean position in the upper chain/glycerol region of the POPC membrane, oriented with its polar carbonyl group towards the aqueous phase. This membrane position is only marginally altered in the presence of cholesterol. A previously reported result that ibuprofen is expelled from the membrane interface in cholesterol-containing DMPC bilayers could not be confirmed.

Two dimensional porous frameworks of graphyne family as therapeutic delivery vehicles for Idarubicin biomolecule in silico: Density functional theory and molecular dynamics simulation

In the present article, transfer efficiency of graphyne's family members as Idarubicin drug delivery systems is evaluated by a combined density functional theory and molecular dynamics simulation approaches in the liquid water. The density functional theory computations such as Non-Covalent Interaction methodology allow the classification of the interatomic interaction of drug molecule with nanosheet as a weak interaction with the adsorption strength value of −81.305 kJ/mol. The density functional theory calculations approve the physical nature of Idarubicin anti-cancer drug interaction with graphydine nanosheet. It is found that graphydine as a good drug delivery vector can carry and deliver Idarubicin drug into the cells without significant changes in the structural and electronic properties of drug molecule in the delivery process. Furthermore, the dynamic behavior of Idarubicin loading on the graphyne-3 nanosheet is investigated utilizing molecular dynamics simulation. It is observed that drug molecules move toward the nanocarrier at the initial time of simulation and adsorb with the parallel orientation relative to the nanosheet surface. Furthermore, molecular dynamics simulation is applied to explore the effects of electric field (magnitude and direction) on the adsorption of Idarubicin drugs on the nanosheet surface. It is found that when the electric field is introduced into the simulation system in z- and xy-directions, the van der Waals interaction energy value shows the increasing trend. In other words, the interaction between the adsorbed drug and nanosheet can be strengthened by applying the electric fields in z- and xy-directions.

Payload delivery of anticancer drug Tegafur with the assistance of graphene oxide nanosheet during biomembrane penetration: Molecular dynamics simulation survey

It is known that the interaction of drug molecules with biomembranes affects their pharmacokinetic parameters. Biological membranes as physical barrier limit diffusion of different types of molecules across the membranes. For that, the drug delivery systems (DDS) are used to increase drug membrane permeability. In this work, the molecular dynamics (MD) simulation is performed to evaluate the mechanism of graphene oxide nanosheet (GO) as Tegafur (TG) drug delivery cargo across the cell membrane. MD simulation shows the spontaneously attraction of GO to the cell membrane during the initial time of simulation. It is found that the complete parallel orientation of nanosheet and further partially its insertion into the membrane is facilitated by increasing the hydrogen bonds (HBs) formation between the oxygen-containing groups of GO and lipid bilayer throughout the simulation trajectory. Molecular dynamics simulation reveals slow release of TG drug molecules from the graphene oxide nanosheet surface near the cell membrane, which highlights the efficiency of GO as a good carrier for the controlled release of Tegafur drug. This study reinforces the consideration of graphene oxide nanosheet for delivering an elevated therapeutic dose directly on the cancer cell target in biomedical applications.