We studied whether the physiological activities of several pharmaceutical products containing the same active ingredient (pantoprazole) can be estimated by the ealier proposed method, which is based on the study of drug effect on the structures of cell membranes (red blood cells, lymphocytes, and platelets) using ESR spectroscopy and spin probes. The properties of one innovator drug and four corresponding generics were compared. There are possible cases when the innovator drug has a higher effect on the structures of blood cell membranes than generics and when the pharmaceutical products have no any effect thereon. In the latter case, the number of side effects is assumed to be minimized.
相似文献Carbon nanotubes (CNTs) constitute an interesting material for nanomedicine applications because of their unique properties, especially their ability to penetrate membranes, to transport drugs specifically and to be easily functionalized. In this work, the energies of the intermolecular interactions of single-walled CNTs and the anticancer drug doxorubicin (DOX) were determined using the AMBER 12 molecular dynamics MM/PBSA and MM/GBSA methods with the aim of better understanding how the structural parameters of the nanotube can improve the interactions with the drug and to determine which structural parameters are more important for increasing the stability of the complexes formed between the CNTs and DOX. The armchair, zigzag, and chiral nanotubes were finite hydrogen-terminated open tubes, and the DOX was encapsulated inside the tube or adsorbed on the nanotube surface. Pentagon/heptagon bumpy defects and polyethylene glycol (PEG) nanotube functionalization were also studied. The best interaction occurred when the drug was located inside the cavity of the nanotube. Armchair and zigzag nanotubes doped with nitrogen, favored interaction with the drug, whereas chiral nanotubes exhibited better drug interactions when having bumpy defects. The π-π stacking and N-H…π electrostatic interactions were important components of the attractive drug-nanotube forces, enabling significant flattening of the nanotube to favor a dual strong interaction with the encapsulated drug, with DOX–CNT equilibrium distances of 3.1–3.9 Å. These results can contribute to the modeling of new drug-nanotube delivery systems.
相似文献In this research, tungsten disulfide (WS2) nanosheets were modified with beta-cyclodextrone (βCD) N-isopropylacrylamide polymers (NIPAAP) for adsorption of tamoxifen (TAM) drug. The synthesized WS2/βCD/NIPAAP samples were characterized by field-emission scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and X-ray diffraction (XRD) analyses. The adsorption experiments of TAM on WS2/βCD/NIPAAP were performed as a function of pH, reaction contact time, temperature and drug concentration. The adsorption kinetic data were well fitted to the pseudo-second-order model. Also, the equilibrium data were well described by Langmuir isotherm model. The maximum adsorption capacity of WS2/βCD/NIPAAP for TAM drug was found to be 62.0 mg/g. The results of regeneration tests showed that the synthesized WS2/βCD/NIPAAP adsorbent can be easily reused after 6 cycles of adsorption–desorption. Furthermore, TAM drug release was investigated in a simulated system with pH 7.4 at different temperatures. The results showed that the release of TAM drug from WS2/βCD/NIPAAP carrier at 50 °C and 37 °C was greater than TAM release at 25 °C. Also, the experimental data of drug release were studied by Higuchi, Ritger-Peppas, zero-order and first-order models. The release data were well fitted to the zero-order model indicating a case II transport. The results showed a high stability for TAM drug.
相似文献Enantioselective analysis or separation is very essential for improved therapeutic effects of drugs as the pure enantiomeric drug formulations display potential benefits over racemates. In this work, we carried out (i) the synthesis of a nanocomposite of β-cyclodextrin and 3D graphene (G/β-CD NC), and (ii) its application for the detection of fluoxetine enantiomers [(RS)-FLX)] using a thin-layer chromatographic method. The synthesized nanocomposite was introduced into silica gel slurry while preparation of thin-layer plates. The separation conditions were optimized by altering pH, temperature, and mobile phase composition. The method is simple and easy to be optimized, and it can therefore be exploited to assess and monitor routine work of enantiomeric purity of drug enantiomers. The average precision (as measured by RSD) was in the region of 1.35‒1.65% for the enantiomers of (RS)-FLX. The measured limit of detection and limit of quantification for (RS)-FLX enantiomers were 1.8 and 5.4 mg mL‒1, respectively.
相似文献The main oral drug absorption barriers are fluid cell membranes, and generally drugs are absorbed by a passive diffusion mechanism. On the other hand, the blood–brain barrier (BBB) is considered to be the main barrier to drug transport into the central nervous system (CNS). The BBB restricts the passive diffusion of many drugs from blood to brain. Biopartitioning micellar chromatography (BMC), a mode of micellar liquid chromatography that uses micellar mobile phases in adequate experimental conditions, can be useful as an in vitro system in mimicking the drug partitioning process into biological systems. In this study, relationships between the BMC retention data of a heterogeneous set of 12 drugs and their pharmacokinetics parameters (human oral drug absorption and BBB penetration ability) are studied and the predictive ability of the models is evaluated. Modeling of log k BMC of these compounds was established by multiple linear regression in two different concentrations (0.07 and 0.09 M) of sodium dodecyl sulfate (SDS). The results showed a fair correlation between human oral drug absorption and BMC retention data in 0.09 M SDS (R 2 = 0.864) and a good correlation between the blood–brain distribution coefficient and BMC retention data in 0.07 M of SDS (R 2 = 0.887). Application of the developed models to a prediction set demonstrated that the model is also reliable with good predictive accuracy. The external and internal validation results showed that the predicted values are in good agreement with the experimental value.
相似文献The basic task of the drug discovery is the establishing of molecular structure of new pharmaceutical agents. To define the molecular structure is only half of the way to new drug. The transport of active molecules to appropriate targets in an organism should be elucidated in details. The selection of polymeric structures playing the role of basis for transport of therapeutic agents into the body is one of the ways to solve the task. Drug loading capacity (DLC) and critical micelle concentration (CMC) are measures of ability of “polymer–micelle” systems to be suitable for the process of the transport of therapeutic agents into an organism. Polymeric micelles are a type of complex multi-phase and multicomponent chemical process and can be used to transport drug into an organism. Prediction of ability of “micelle–polymer” systems to be a tool for transport of therapeutic agents to targets in organism is an important task. Models, which are a mathematical function of available eclectic information about architecture of micelles and polymers, are suggested. The eclectic data are represented via the so-called quasi-simplified molecular input-line entry system (SMILES), which are analogy of traditional SMILES. The quasi-SMILES contain some additional information besides the molecular architecture (physicochemical and biochemical conditions). Predictive potential of these models is good.
相似文献Blood spot collection cards can be easily used to obtain specimens for analysis of drugs for the purpose of therapeutic drug monitoring. In this work, the development and validation of a simple technique for the determination of lamotrigine from dried blood spots is described. The method is based on liquid chromatography with ultraviolet detection. The intra- and inter-day precision (measured by CV%) was less than 11%. The accuracy (measured by relative error %) was less than 12%. The limits of detection and quantification were calculated to be 0.12 and 0.2 μg mL−1 respectively. The small volume of blood required (10 μL), the short analysis time (less than 4 min), combined with the simplicity of the analytical technique makes this a useful procedure for monitoring lamotrigine concentrations. Our preliminary experience with the developed method indicated that it can be implemented in routine clinical setting.
相似文献Chitosan is a biopolymer that forms hydrogels after swell in acid medium. The environment of the three-dimensional network of the chitosan-based hydrogels can be modified by its degree of swelling and crosslinking. In this way, nicotine was incorporated in the hydrogel formulations, with or without crosslinking with glutaraldehyde (0.01%), in different swollen states. Transdermal delivery of nicotine by chitosan-based hydrogels was studied in order to achieve the prolonged administration of the drug. Thermal analysis indicated a preliminary stability of these formulations, and the mechanism of drug release from hydrogels was dependent of the swelling degree and crosslinking. These formulations were able to control the transdermal flux of nicotine for up to 48 h following zero-order kinetics. The hydrogels with higher amounts of water or the partially dried crosslinked hydrogels reduced the partition of nicotine into the skin, leading to a minor transdermal flux of the drug (<3.4 µg cm−2 h−1). On the other hand, the partially dried non-crosslinked hydrogels lead to a major transdermal flux of the drug (20.19 µg cm−2 h−1) due to modifications of the environment into the hydrogel. In this way, these transdermal formulations were promising vehicles for prolonged administration of nicotine.
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