Presence Of Drug Molecules Research Articles

Colorimetric detection of Pd2+ and Ni2+ ions using a probe having benzo[d]imidazo[2,1-b]thiazole and pyrene rings: Application in detection of Pd2+ ion in anti-hypertensive drugs

Pd-complexes are widely used in the pharmaceutical industry to synthesize APIs and drug molecules. It is imperative to detect even trace amounts of Pd impurities in them. A probe (E/Z)-N'-(pyren-1-ylmethylene)benzo[d]imidazo[2,1-b]thiazole-2-carbohydrazide (LH) having benzo[d]imidazo[2,1-b]thiazole and pyrene rings has been synthesized. LH was found to exhibit a change from colourless to yellowish green in presence of Pd2+ and Ni2+ ions. This colorimetric “turn on” response has also been observed with Pd2+ ions in the presence of “sartan” drugs, namely telmisartan, valsartan, irbesartan, olmesartan medoxomil and losartan potassium. The limit of detection ranged from 46.1 to 93.9 nM (4.9 to 6.0 ppb) for PdCl2 and 10.6 to 19.6 nM (1.1 to 2.1 ppb) for Pd(PPh3)2Cl2 and these are lower than the limit suggested by the EMA. The LOD values of Ni2+ ion was 9.301 nM which is also lower than the WHO guideline value. This probe showed a remarkable ability to recover Pd2+ ions from the spiked solution of drug samples. The probe formed stable 1:1 complexes with both the metal ions with binding constant values 3.72 × 103 L mol−1 (for Pd2+) and 8.26 × 104 L mol−1 (for Ni2+). Binding constant values of Pd-L complex increased in the presence of drug molecules, thereby indicating the absence of interference. The pH tolerance of the probe was found to be in the range of 3–11 (for Ni2+) and 2–11 (for Pd2+). DFT/TDDFT studies performed on LH, [Pd(L)(CH3CN)Cl] and [Ni(LH)(H2O)(CH3CN)Cl2] in CPCM continuum solvation model in CH3CN, showed good correlation between calculated UV–Vis and experimental spectra.

Ultrasonic assisted in situ mineralization of hydroxyapatite nanoparticles in the presence of drug molecule: An insight on biowaste derived materials for the local drug delivery

The fabrication of local drug delivery systems having an osteoconductive property with sustained drug release ability has been a hot topic of research interest. The goal of this research is to employ ultrasonic-assisted in situ mineralization of HAp nanoparticles in the presence of ciprofloxacin utilizing eggshells as a calcium precursor. Analysis of the prepared samples using XRD, FTIR, EDX, TGA, and TEM confirmed the in situ loading of ciprofloxacin on HAp nanoparticles. Moreover, the prepared samples exhibit mesoporous characteristics and contain bioactive components such as Mg and carbonate ions which were inherited from an eggshell source. The ciprofloxacin loading efficiency and amount of ciprofloxacin loaded in the Cip-HAp were found to be 63 % and 5 %, respectively, based on UV–visible spectroscopic characterization and thermogravimetric analysis. Furthermore, ciprofloxacin release from the prepared sample was found to be sustained and prolonged for 30 days with a 90 % drug release profile. The ciprofloxacin release data fitted the Higuchi model and Ritger-Peppas model and indicated that the Fickian diffusion process involved the drug release kinetics. In situ preparation of HAp nanoparticles in the presence of ciprofloxacin result in a strong interaction between ciprofloxacin and HAp and tend to result in a drug carrier delivery system with a prolonged and continuous release that could be used to treat osteomyelitis. Moreover, preparing HAp nanoparticles using eggshell calcium precursor is an economical and environmentally friendly method that reduces production costs.

Interaction of Amoxicillin with DOPC layer

This paper reports the investigations on the interaction of antibiotic drug Amoxicillin (AMX) and DOPC lipid layer. The interactions between DOPC and AMX are studied with Langmuir-Blodgett (LB) technique and Brewster Angle Microscopy (BAM). π-A isotherm and BAM studies confirm the incorporation of Amoxicillin onto DOPC membrane. The membrane fluidity as well as elasticity have been affected by the incorporation of drug molecules. AMX molecules enhance the fluid nature of the DOPC membrane. BAM study was employed to visualize the in-situ membrane structure in absence and presence of drug molecules. As a whole this investigation helped to have idea about physical changes in the biomembrane when interacted with drug molecules.

Effects of selective calcium channel blockers on ions’ permeation through the human Cav1.2 ion channel: A computational study

Selective calcium channel antagonists are widely used in the treatment of cardiovascular disorders. They are mainly classified into 1,4-dihydropyridine (1,4-DHPs) and non-DHPs. The non-DHPs class is further classified into phenylalkylamines (PAAs) and benzothiazepines (BZTs) derivatives. These blockers are used for the treatment of hypertension, angina pectoris, and cardiac arrhythmias. Despite their well-established efficiency, the structural basis behind their activity is not very clear. Here we report the use of a near-open confirmation (NOC) model of the Cav1.2 cardiac ion channel to examine the mode of binding of these antagonists within the pore domain as well as the fenestration of the pore-forming domains. Effects of calcium ion permeation in the presence of drug molecules were assessed using steered molecular dynamics (SMD) simulations. These studies reveal that nicardipine, a DHP derivative, shows a strong Cav1.2 blocking activity, requiring more 2500 pN force to pull calcium ion towards the channel’s pore in the presence of the compound. Similar blocking activity was observed for verapamil, a PAA derivative, requiring almost 2300 pN of force. The least blocking activity was observed for Diltiazem, a BZT derivative. Our results explain the structural basis and the binding details of 1,4-DHPs, PAAs and BZTs at their distinct Cav1.2 sites and offer detailed insights into their mechanism of action in modulating the Cav1.2 channel.

Synthesis and Physico-chemical Characterization of Nanohybrid Materials Based on Isonicotinic Acid Hydrazide

The usual treatment for tuberculosis is difficult by its long-term therapy, raised dosing frequency and adverse effects of anti-tuberculosis drugs. Anionic clays, also called layered double hydroxides are a class of hydrotalcite like structures having high compositional variety and being able to self-assembly in the presence of drug molecules. The work refers to the development of nanohybrid materials like delivery systems that intercalates isonicotinic acid hydrazide, known as isoniazid anti-tuberculosis drug, into layered structure of hydrotalcite compounds. Loaded drug molecules of isoniazid were proved to be released in a controlled way from the as synthesized nanostructure in a simulated buffer solution. The obtained sample was characterized by advanced techniques thus demonstrating the inclusion of isoniazid antibiotic between hydrotalcite sheets. These results revealed important expectations for further researches of these organic-inorganic nanocomposites for tuberculosis treatment.

Inflammation-responsive self-regulated drug release from ultrathin hydrogel coating

Heterotopic ossification(HO) is a potential severe complication after many biomaterial implanting surgeries, and the inflammation environment caused by the implanting-associated infections is considered as the main nosogenesis. Herein, an inflammation-responsive drug release system was designed by chemically conjugating indometacin (via ester group) onto hydrogel coating to realize local self-regulated drug release to prevent HO. In our strategy, poly(3-mercaptopropyl)trimethoxysilane-co-acrylic acrylate and polyvinyl alcohol (providing anchoring sites for drug molecules) were firstly synthesized and functionalized with ene-groups, then a hydrogel layer was formed and covalently attached onto thiol-modified substrate via thiol-ene click chemistry, followed by grafting indometacin. A porous structure of the attached hydrogel layer was observed by scanning electron microscopy, and the presence of drug molecules in the hydrogel layer was confirmed by X-ray photoelectron spectroscopy and UV–vis absorption spectra. The drug release could be triggered under the mimicking inflammation environment, and the release rate was responsive to the inflammation degree. In addition, after attaching the hydrogel coating, the substrate showed low cytotoxicity, and high promotion for cell adhesion and proliferation. The excellent hemocompatibility of the hydrogel coating was also demonstrated by prolonged clotting time and suppressed platelet adhesion. This work suggests that the inflammation-responsive indometacin conjugated hydrogel coating has great potential to be used for prophylaxis HO.

Controlled Release of Nor-β-lapachone by PLGA Microparticles: A Strategy for Improving Cytotoxicity against Prostate Cancer Cells.

Prostate cancer is one of the most common malignant tumors in males and it has become a major worldwide public health problem. This study characterizes the encapsulation of Nor-β-lapachone (NβL) in poly(d,l-lactide-co-glycolide) (PLGA) microcapsules and evaluates the cytotoxicity of the resulting drug-loaded system against metastatic prostate cancer cells. The microcapsules presented appropriate morphological features and the presence of drug molecules in the microcapsules was confirmed by different methods. Spherical microcapsules with a size range of 1.03 ± 0.46 μm were produced with an encapsulation efficiency of approximately 19%. Classical molecular dynamics calculations provided an estimate of the typical adsorption energies of NβL on PLGA. Finally, the cytotoxic activity of NβL against PC3M human prostate cancer cells was demonstrated to be significantly enhanced when delivered by PLGA microcapsules in comparison with the free drug.

Smart montmorillonite-polypyrrole scaffolds for electro-responsive drug release

Hybrids of montmorillonite (Mt) and polypyrrole (PPy) were prepared by in situ electropolymerization of pyrrole monomer in the dispersion of Mt in the presence of drug molecules (aspirin), and aspirin anions were incorporated into the Mt-PPy hybrids as dopants. The resulting drug loaded Mt-PPy was characterized by field emission scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy (FT-IR), electrochemical impedance spectroscopy (EIS), and X-ray powder diffractometer (XRD). The Mt-PPy hybrids combined the advantages of Mt (relatively large specific surface area) and electro-responsive feature of PPy, which was applied as an electrically tunable drug release platform. Compared with PPy, the electro-stimulated drug release behaviors were significantly enhanced at the Mt-PPy hybrids, indicating that the proposed electro-responsive hybrids might be a promising candidate for smart and intelligent drug release.

The adsorptive removal of a cationic drug from aqueous solution using poly (methacrylic acid) hydrogels

This study describes adsorptive removal of the antibiotic drug ciprofloxacin hydrochloride from simulated water using poly(methacrylic acid) (PMAA) as adsorbent. The adsorbent was characterised by various instrumental techniques such as X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) spectroscopy. The adsorption equilibrium data, as studied at 3 temperatures, namely, 15, 25 and 37°C, were best interpreted by the Langmuir adsorption isotherm model. Moreover, an increase in temperature reduces drug uptake. A pH of the adsorption system in the range of 5.0 to 8.0 causes maximum adsorption of the drug. The presence of drug molecules in the adsorbent particles was shown by various techniques: X-ray diffraction (XRD), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) analysis. Antibacterial studies also reveal the adsorption of the drug from solution.Keywords: Adsorption, ciprofloxacin, Langmuir isotherm, X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy

Problems in Ophthalmic Drug Delivery: Evaluation of the Interaction Between Preservatives and Cyclodextrins

Background: Today, the use of cyclodextrins (CDs) is a major concern in drug formulations to improve solubility and stability of compounds. It has been known that CDs can reduce the antimicrobial effectiveness of preservatives by formation of inclusion complexes. Objectives: In this study the interaction between commonly used preservatives, benzalkonium chloride (BZCl) or methyl paraben (MP), with synthetic CDs (HP ?-CD or SBE ?-CD) in the presence or absence of ethylene diamine tetra acetic acid (EDTA), as a preservative potentiator, and fluorometholone was investigated. Materials and Methods: The tests were performed during a 4 week period according to the preservative effectiveness test of USP 2010. Results: The results showed that CDs reduce the effectiveness of BZCl and MP even in the presence of drug molecules. The only exception was HP ?-CD 5% solution with BZCl and EDTA which was effective against tested microorganisms both in the presence and absence of drug molecules. Conclusions: The solution of HP ?-CD 5% with BZCl 0.02% and EDTA 0.1% was selected as a good carrier for dissolving fluorometholone for use as an eye drop.

Encapsulation of Hydrophobic Drugs in Pluronic F127 Micelles: Effects of Drug Hydrophobicity, Solution Temperature, and pH

Three drugs, ibuprofen, aspirin, and erythromycin, are encapsulated in spherical Pluronic F127 micelles. The shapes and the size distributions of the micelles in dilute, aqueous solutions, with and without drugs, are ascertained using cryo-scanning electron microscopy and dynamic light scattering (DLS) experiments, respectively. Uptake of drugs above a threshold concentration is seen to reduce the critical micellization temperature of the solution. The mean hydrodynamic radii and polydispersities of the micelles are found to increase with decrease in temperature and in the presence of drug molecules. The hydration of the micellar core at lower temperatures is verified using fluorescence measurements. Increasing solution pH leads to the ionization of the drugs incorporated in the micellar cores. This causes rupture of the micelles and release of the drugs into the solution at the highest solution pH value of 11.36 investigated here and is studied using DLS and fluorescence spectrocopy.

Evaluating interaction forces between BSA and rabbit anti-BSA in sulphathiazole sodium, tylosin and levofloxacin solution by AFM

Protein-protein interactions play crucial roles in numerous biological processes. However, it is still challenging to evaluate the protein-protein interactions, such as antigen and antibody, in the presence of drug molecules in physiological liquid. In this study, the interaction between bovine serum albumin (BSA) and rabbit anti-BSA was investigated using atomic force microscopy (AFM) in the presence of various antimicrobial drugs (sulphathiazole sodium, tylosin and levofloxacin) under physiological condition. The results show that increasing the concentration of tylosin decreased the single-molecule-specific force between BSA and rabbit anti-BSA. As for sulphathiazole sodium, it dramatically decreased the specific force at a certain critical concentration, but increased the nonspecific force as its concentration increasing. In addition, the presence of levofloxacin did not greatly influence either the specific or nonspecific force. Collectively, these results suggest that these three drugs may adopt different mechanisms to affect the interaction force between BSA and rabbit anti-BSA. These findings may enhance our understanding of antigen/antibody binding processes in the presence of drug molecules, and hence indicate that AFM could be helpful in the design and screening of drugs-modulating protein-protein interaction processes.

Experimental investigation on blood magnetic contamination in the presence of drug molecules

The purpose of the present project was to study the interference of magnetic nanoparticles with drug molecules – rifampicin, used in lung infectious disease and respectively, sodium diclofenac, an antiinflammatory steroid. The controlled magnetic contamination was accomplished using colloidal nanoparticles supplied from diluted magnetic fluids. Various concentrations of diluted aqueous magnetic fluids, based on magnetite cores coated with citric acid and respectively sodium oleate, were tested. The experiment was focused on the capacity of the magnetic nanoparticles to form reversible complexes with the drug molecules, as well as on the monitoring of the nanoparticle-drug complex dynamics, under the action of external magnetic field. The level of released rifampicin ranged between 4 mg/100 ml and 7 mg/100 ml for the magnetic exposure of 20 mT, while the sodium diclofenac decomplexation level was not higher than 2.5 mg/100 ml under magnetic exposure of 60 mT. The experimental arrangement was proved to be an adequate model for the dynamical study of magnetite reversible complexation with drug molecules, evidencing certain specific values of drug concentration and magnetic field induction that favour such interactions.

Dispersion polymerization of vinyl monomers in supercritical carbon dioxide in the presence of drug molecules: A one‐pot route for the preparation of controlled delivery systems

AbstractThe polymerization of 1‐vinyl‐2‐pyrrolidone in supercritical carbon dioxide in the presence of ibuprofen as a model drug was investigated as a new one‐pot process for the preparation of polymer‐based drug delivery systems (DDSs). The composites were prepared at 65 °C and P = 31–42 MPa by changing the initial concentration of the drug and the concentration of a crosslinking agent and that of a hydrophobic comonomer. The effects of these parameters on the performances of the polymerization and on the in vitro release kinetics of ibuprofen were studied. In all the experiments, part of the drug was entrapped inside the polymer particles and dissolved more slowly with respect to the pure compound. Copolymerization with methyl methacrylate was the most effective route to obtain a DDS with sustained temporal release of the drug molecule. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7429–7446, 2008

Biphasic nature of the binding of cationic amphipaths with artificial and biological membranes

We have studied the interaction with liposomes and red cell membrane of various cationic amphipaths, chlorpromazine, methochlorpromazine, imipramine and propranolol. At low concentrations the interaction is a partition of the molecule between the lipid hydrophobic phase and the aqueous medium. The extent of the partition is dependent on the membrane composition or physical properties, on the incubation conditions (pH, ions) and on the amphipath used. After a given amount of amphipath has entered in the membrane, a new type of interaction appears which leads to an apparent saturable association. This association, which probably involves the anionic groups of the membrane components, might result from structural or/and electrical membrane perturbations induced by the presence of drug molecules between the phospholipids. Thus the interaction of a molecule of cationic amphipath with a membrane varies according to the amount of drug present.