Redetermination of germacrone type II based on single-crystal X-ray data.

The extraction and purification procedures, crystallization and crystal structure refinement (single-crystal X-ray data) of germacrone type II, C15H22O, are presented. The structural results are compared with a previous powder X-ray synchrotron study [Kaduk et al. (2022 ▸). Powder Diffr. 37, 98-104], revealing significant improvements in terms of accuracy and precision. Hirshfeld atom refinement (HAR), as well as Hirshfeld surface analysis, give insight into the inter-molecular inter-actions of germacrone type II.

Exploring the Potential of a Novel Iodine-Based Material as an Alternative Contrast Agent in X-ray Imaging Studies.

BACKGROUND: Contrast-enhanced mammography is one of the new emerging imaging techniques used for detecting breast tissue lesions. Optimization of imaging protocols and reconstruction techniques for this modality, however, requires the involvement of physical phantoms. Their development is related to the use of radiocontrast agents. This study assesses the X-ray properties of a novel contrast material in clinical settings. This material is intended for experimental use with physical phantoms, offering an alternative to commonly available radiocontrast agents. MATERIALS AND METHODS: The water-soluble sodium salt of the newly synthesized diiodine-substituted natural eudesmic acid, Sodium 2,6-DiIodo-3,4,5-TriMethoxyBenzoate [NaDITMB], has been investigated with respect to one of the most commonly applied radiocontrast medium in medical practice-Omnipaque®. For this purpose, simulation and experimental studies were carried out with a computational phantom and a physical counterpart, respectively. Synthetic and experimental X-ray images were subsequently produced under varying beam kilovoltage peaks (kVps), and the proposed contrast material was evaluated. RESULTS AND DISCUSSION: Simulation results revealed equivalent absorptions between the two simulated radiocontrast agents. Experimental findings supported these simulations, showing a maximum deviation of 3.7% between the image gray values of contrast materials for NaDITMB and Omnipaque solutions for a 46 kVp X-ray beam. Higher kVp X-ray beams show even smaller deviations in the mean grey values of the imaged contrast agents, with the NaDITMB solution demonstrating less than a 2% deviation compared to Omnipaque. CONCLUSION: The proposed contrast agent is a suitable candidate for use in experimental work related to contrast-enhanced imaging by utilizing phantoms. It boasts the advantages of easy synthesis and is recognized for its safety, ensuring a secure environment for both the experimenter and the environment.

2,6-Di-bromo-3,4,5-tri-meth-oxy-benzoic acid.

The title compound, 2,6-di-bromo-3,4,5-tri-meth-oxy-benzoic acid (DBrTMBA), C10H10Br2O5, was obtained by bromination and transhalogenation of 2-iodo-3,4,5-tri-meth-oxy-benzoic acid with KBrO3. Like the previously reported 2,6-di-iodo-3,4,5-tri-meth-oxy-benzoic acid (DITMBA), the structure of the title compound features a catemeric arrangement of DBrTMBA mol-ecules along an endless chain of carb-oxy-lic H-carbonyl inter-actions. A short carbon-yl-phenyl contact hints at a possible lone pair(O)-π-hole inter-action further stabilizing the chain-like structure over a dimeric arrangement of the carb-oxy-lic acid.

Chlorhexidine-Silver Nanoparticle Conjugation Leading to Antimicrobial Synergism but Enhanced Cytotoxicity.

This study explored the potential synergism within chlorhexidine-silver nanoparticle conjugates against Influenza type A, Staphylococcus aureus, Escherichia coli, and Candida albicans. Silver nanoparticles (SN) were obtained by the reduction of silver ions with green tea total phenolic extract and conjugated with chlorhexidine (Cx). The particles were characterized by UV-Vis and FTIR spectroscopies, dynamic light scattering, X-ray diffraction, and transmission electron microscopy. A stable negatively charged nano-silver colloid (ζ = -50.01) was obtained with an average hydrodynamic diameter of 92.34 nm. In the presence of chlorhexidine, the spectral data and the shift of the zeta potential to positive values (ζ = +44.59) revealed the successful sorption of the drug onto the silver surface. The conjugates (SN-Cx) demonstrated potentiation in their effects against S. aureus and C. albicans and synergism against E. coli with minimal inhibitory concentrations of SN at 5.5 µg/mL + Cx 8.8 µg/mL. The SN showed excellent virucidal properties, increasing with time, and demonstrated low toxicity. However, the coupling of the cationic chlorhexidine with nano-silver did not reduce its intrinsic cytotoxicity on various cell lines (MDCK, BJ, and A549). The newly synthesized antimicrobial agent exhibited an extended and promising therapeutic spectrum and needs to be further evaluated regarding the designated route of administration in three-dimensional cell models (e.g., nasal, bronchial, dermal, ocular, etc.).

Bigel Formulations of Nanoencapsulated St. John's Wort Extract-An Approach for Enhanced Wound Healing.

This study aimed to develop a semisolid vehicle for topical delivery of nanoencapsulated St. John's wort (SJW) extract, rich in hyperforin (HP), and explore its wound-healing potential. Four nanostructured lipid carriers (NLCs) were obtained: blank and HP-rich SJW extract-loaded (HP-NLC). They comprised glyceryl behenate (GB) as a solid lipid, almond oil (AO), or borage oil (BO) representing the liquid lipid, along with polyoxyethylene (20) sorbitan monooleate (PSMO) and sorbitan monooleate (SMO) as surfactants. The dispersions demonstrated anisometric nanoscale particles with acceptable size distribution and disrupted crystalline structure, providing entrapment capacity higher than 70%. The carrier exhibiting preferable characteristics (HP-NLC2) was gelled with Poloxamer 407 (PM407) to serve as the hydrophilic phase of a bigel, to which the combination of BO and sorbitan monostearate (SMS) organogel was added. The eight prepared bigels with different proportions (blank and nanodispersion-loaded) were characterized rheologically and texturally to investigate the impact of the hydrogel-to-oleogel ratio. The therapeutic potential of the superior formulation (HP-NLC-BG2) was evaluated in vivo on Wistar male rats through the tensile strength test on a primary-closed incised wound. Compared with a commercial herbal semisolid and a control group, the highest tear resistance (7.764 ± 0.13 N) was achieved by HP-NLC-BG2, proving its outstanding wound-healing effect.

Intercriteria Analysis to Diagnose the Reasons for Increased Fouling in a Commercial Ebullated Bed Vacuum Residue Hydrocracker.

The intercriteria analysis developed on the base of intuitionistic fuzziness and index matrices was applied to evaluate processing data of the LUKOIL Neftohim Burgas H-Oil ebullated bed vacuum residue hydrocracker with the aim of revealing the reasons for increased fouling registered during the 3rd cycle of the H-Oil hydrocracker. It was found that when the ratio of the ΔT of the 1st reactor to the ΔT of the 2nd reactor gets lower than 2.0, an excessive H-Oil equipment fouling occurs. The fouling was also found to be favored by processing of lower Conradson carbon content vacuum residual oils and increased throughput and depressed by increasing the dosage of the HCAT nanodispersed catalyst. The fouling in the atmospheric tower bottom section is facilitated by a lower aromatic content in the atmospheric tower bottom product. The addition of FCC slurry oil not only increases aromatic content but also dissolves some of the asphaltenes in the atmospheric residual hydrocracked oil and decreases its colloidal instability index. The fouling in the vacuum tower bottom section is facilitated by a higher saturate content in the VTB. Surprisingly, it was found that the asphaltene content in the VTB depresses the fouling rate. No relation was found of the sediment content in the hydrocracked residual oils measured by hot filtration tests and by the centrifuge method to the equipment fouling of the H-Oil hydrocracker.

Ammonio Methacrylate Copolymer (Type B)-Diltiazem Interactions in Solid Dispersions and Microsponge Drug-Delivery Systems.

This paper presents a complex analytical study on the distribution, solubility, amorphization, and compatibility of diltiazem within the composition of Eudragit RS 100-based particles of microspongeous type. For this purpose, a methodology combining attenuated total reflectance Fourier transform infrared (ATR-FTIR) absorption spectroscopy, differential scanning calorimetry (DSC), scanning electron microscopy with energy-dispersive X-ray microanalysis (SEM-EDX), and in vitro dissolution study is proposed. The correct interpretation of the FTIR and drug-dissolution results was guaranteed by the implementation of two contrasting reference models: physical drug-polymer mixtures and casting-obtained, molecularly dispersed drug-polymer composites (solid dispersions). The spectral behavior of the drug-polymer composites in the carbonyl frequency (νCO) region was used as a quality marker for the degree of their interaction/mutual solubility. A spectral-pattern similarity between the microsponge particles and the solid dispersions indicated the molecular-type dispersion of the former. The comparative drug-desorption study and the qualitative observations over the DSC and SEM-EDX results confirmed the successful synthesis of a homogeneous coamorphous microsponge-type formulation with excellent drug-loading capacity and "controlled" dissolution profile. Among them, the drug-delivery particles with 25% diltiazem content (M-25) were recognized as the most promising, with the highest population of drug molecules in the polymer bulk and the most suitable desorption profile. Furthermore, an economical and effective analytical algorithm was developed for the comprehensive physicochemical characterization of complex delivery systems of this kind.

A small-scale method of sample preparation suitable for simultaneous HPLC-UV assay of capecitabine and its 5'-DFCR metabolite in mouse blood plasma

Abstract The objective of the study was to develop an easy, cheap, effective, and safe, small-scale method for sample preparation suitable for the simultaneous high-performance liquid chromatography (HPLC)-ultraviolet (UV) assay of capecitabine and its 5′-deoxy-5-fluorocytidine (5′-DFCR) metabolite in mouse blood plasma. The suitability of the proposed method of sample preparation was verified by the optimal effectiveness and efficiency achieved in the overall analytical workflow. The chromatographic separation of capecitabine and its first metabolite was performed on a Hypersil GOLD aQ column with a mobile phase consisting of 1% formic acid, methanol, and water, and run in a gradient elution mode. The absence of interfering endogenous components at the retention times of each analyte was confirmed by the chromatographic analysis of blank matrices and matrices spiked with the corresponding standards. The absence of any tactile matrix effect was also recorded. For the first time, the effect of the vacutainer's anticoagulant on the extraction efficiency of both analytes was evaluated. The method was found to be accurate, precise, and specific. The estimated mean "extraction" efficiencies were ≥90% for each analyte. The lower limit of quantitation for both capecitabine and 5′-DFCR was 0.05 μg/mL.

A QCM-based assay of drug content in Eudragit RS 100-based delivery systems.

A specific version of the quartz crystal microbalance method has been proposed for quantitative evaluation of drug content in polymeric drug carrier systems. In this study, ammonio methacrylate copolymer (type B) microparticles and their standard solutions have been prepared and loaded with set amounts of the medications diltiazem (base) and lidocaine. The analytes have been segregatim deposited on the surface of the resonator and the drug content in them has been derived from the downshift of the resonance frequency produced by irreversible interaction of the drug molecules with irradiating hydrochloric gas. The obtained results have been statistically processed on a number of samples and have been found to exhibit excellent coherence to set theoretical values. As an alternative, the conventional pharmacopoeial UV-Vis spectral method has also been separately applied to studied samples, revealing worsened performance in the case of lidocaine due to polymer matrix interference. Thus the universality of the QCM method has been proved to add to its versatility and precision. The method appears to be readily applicable to the routine pharmaceutical quantity control of bulk and multiparticulate drug forms.

In vitro and ex vivo studies on diltiazem hydrochloride-loaded microsponges in rectal gels for chronic anal fissures treatment.

Diltiazem hydrochloride, topically applied at 2% concentration, is considered effective for the treatment of chronic anal fissures, although it involves several side effects among which anal pruritus and postural hypotension. To test the hypothesis that a sustained delivery system of diltiazem hydrochloride may be helpful for the treatment of chronic anal fissures, in the present study we evaluated the potential of gels containing diltiazem hydrochloride entrapped in microsponges. Such microsponges were based on Eudragit RS 100 and the effect of some formulation variables was assessed by a 23 full factorial screening design. An optimized formulation of diltiazem hydrochloride microsponges was dispersed in Methylcellulose 2% or Poloxamer 407 20% and the resulting gels (micro-l-diltiazem hydrochloride 2%) were subjected to in vitro drug release, ex vivo permeability and drug deposition after application on porcine rectal mucosa. The results showed a prolonged release up to 24 h from micro-l-diltiazem hydrochloride at 2% in the gels. The permeation tests revealed up to 18% higher drug retention on the mucosal tissue after 24 h by the micro-l-diltiazem hydrochloride 2% gels compared to conventional diltiazem hydrochloride gels at 2%. These results suggest that diltiazem hydrochloride-loaded microsponges dispersed in rectal gels may be useful to overcome some limitations of conventional local chronic anal fissure therapy.

Growth and toxic gas sensing properties of poly(urethaneimide) thin films.

In this work we present a study on the growth and the gas sensing properties of poly(urethane imide) thin films. We first deeply characterized by atomic force microscopy (AFM) the nanostructuration of the poly(urethane imide) holding different amine groups. We further studied the interaction between highly toxic gases such as hexamethyleneimine (HMI) and pyridine and the polymer by using an unconventional method based on Quartz Crystal Microbalance (QCM) measurement. We showed for the first time that weak interactions, i.e. hydrogen bonding between the gas molecules and the polymer film allow the diffusion of the gas molecule deep in the polymeric film and the recovery of the film once the gas molecules leave the sensor. This first work paves a new way for the design of a completely recoverable sensor able to detect highly toxic gases for environmental concern.

Carboxylic modified spherical mesoporous silicas аs drug delivery carriers.

The present study deals with the development and functionalization of mesoporous silica nanoparticles as drug delivery platforms. Spherical MCM-41 and SBA-15 silicas with different pore sizes (2.7 nm and 5.5 nm, respectively) were post-synthesis modified applying a new, two step process. The initial step was the modification with 3-amino-propyltriethoxysilane, and the next was the reaction with succinic anhydride in toluene in order to obtain carboxylic modified mesoporous carriers. The carboxylic-functionalized mesoporous materials were characterized by XRD, nitrogen physisorption, TEM, ATR FT-IR spectroscopy. The successful carboxylic functionalization was proved by the changes of the zeta potential of the mesoporous materials before and after modification. The parent and the carboxylic-modified MCM-41 and SBA-15 materials showed high adsorption capacity (approximately 50 wt.%, except for non-functionalized MCM-41) for sulfadiazine that possesses amino functional groups. Mesoporous structure peculiarities lead to different adsorption capacities on the carriers. In vitro release studies showed slower release rate of sulfadiazine from carboxylic modified MCM-41 and SBA-15 mesoporous particles compared to the non modified ones. Both non loaded and drug-loaded silica materials demonstrated no cytotoxicity on Caco-2 cell line. The functionalized mesoporous systems are appropriate drug delivery platforms due to their biocompatibility and the possibility to modify drug release.

Synthesis of amphiphilic [PEO(PCL)2] triarm star-shaped block copolymers: a promising system for in cell delivery.

The paper reports on a simple method of synthesizing [PEO(PCL)(2)] triarm star-shaped copolymers by a combination of Michael-addition type reaction and ring-opening polymerization. A Michael-addition reaction yielded a PEO end-capped by two hydroxyl groups-a [PEO(OH)(2)] macroinitiator-which was used for sequential building of PCL blocks. The macroinitiator and copolymers were analyzed by FTIR, (1)H NMR spectroscopy and SEC. The self-assembly behavior of the copolymers in aqueous media was studied by UV-Vis spectroscopy. The size and morphology of the obtained micelles were determined by TEM. None of the polymers had cytotoxic effects in vitro. Cellular uptake studies showed the accumulation of neutral red loaded micelles in the perinuclear area of human hepatocellular carcinoma cells revealing a cellular uptake associated with macropinocytosis and caveolae mediated endocytosis. The accumulation had a sustained effect over 3 days pointing at the potential application of the copolymers micelles as a drug delivery system.