Dissolvable Carboxymethylcellulose Microneedles for Noninvasive and Rapid Administration of Diclofenac Sodium

The aim of this study is to prepare dissolvable biopolymeric microneedle (MN) patches composed solely of sodium carboxymethylcellulose (CMC), a water-soluble cellulose derivative with good film-forming ability, by micromolding technology for the transdermal delivery of diclofenac sodium salt (DCF). The MNs with ≈456 µm in height displayed adequate morphology, thermal stability up to 200 °C, and the required mechanical strength for skin insertion (>0.15 N needle⁻¹). Experiments in ex vivo abdominal human skin demonstrate the insertion capability of the CMC_DCF MNs up to 401 µm in depth. The dissolution of the patches in saline buffer results in a maximum cumulative release of 98% of diclofenac after 40 min, and insertion in a skin simulant reveals that all MNs completely dissolve within 10 min. Moreover, the MN patches are noncytotoxic toward human keratinocytes. These results suggest that the MN patches produced with CMC are promising biopolymeric systems for the rapid administration of DCF in a minimally invasive manner.     

Interaction of human plasma fibrinogen with commercially pure titanium as studied with atomic force microscopy and X-ray photoelectron spectroscopy

The surface of a biomaterial interacts with the body fluid upon implantation in the human body. The biocompatibility of a material is strongly influenced by the adsorption of proteins onto the surface. Titanium is frequently used as a biomaterial for implants in orthopedics and cardiovascular devices. Understanding the biocompatibility is very important to improve implants. The surface chemistry of an implant material and its influence on the interaction with body fluid is crucial in that perspective. The main goal of this study was to investigate the conformation of human plasma fibrinogen (HPF) adsorbed on commercially pure titanium (CP Ti) on a molecular level by means of ex situ atomic force microscopy (AFM). With X-ray photoelectron spectroscopy combined with argon ion beam depth profiling, it was shown that the oxide layer present at the surface was mainly composed of TiO2, with a small percentage of Ti2O3. Ex situ AFM imaging showed the conformation of HPF on CP Ti. Single molecules and aggregates of fibrinogen were observed. The trinodular structure of single HPF molecules (two spherical D domains at the distal ends of the extended molecule and the central spherical E domain) adsorbed onto CP Ti was visualized. Aggregate formation through the connection of the D domains of the HPF molecules was observed on CP Ti. The alphaC domains of HPF were not visible on CP Ti. The ex situ AFM images indicated conformational changes of HPF upon adsorption onto CP Ti. The conformation of the adsorbed HPF molecules was different on mica and titanium. The difference in wettability between both substrates caused a larger spread of the protein on the CP Ti surface and thus resulted in a larger perturbation to the native structure of HPF as compared to mica.     

Sol–gel synthesis and structure of silica hybrid materials

In this work the research results on the sol–gel synthesis and structure of silica nanocomposites, containing carrageenan and their application as carriers for cell immobilization were described. The samples were prepared at room temperature by replacing different quantity of the inorganic precursor with κ-carrageenan. For studying the structure of the synthesized hybrids the following methods were used: FT-IR, XRD, BET-Analysis, SEM, AFM and Roughness Analysis. The influence of the type of silicon precursors, nature and quantity of organic component on the structure, surface area, design and size of nanostructures was established. The possibility of application of the synthesized biocatalysts in an enzyme degradation process of the toxic, carcinogenic and mutagenic substances benzonitrile, fumaronitrile, o-, m-, and p-tolunitriles was investigated at batch experiments. A two-step biodegradation process in a column bioreactor of fumaronitrile was followed. After operation of the system for 8 h at a flow rate 45 mL h^?1 and at 60 °C, the overall conversion was 89%, showing a good stability of the developed process.     

Detection of the administration of 17beta-nortestosterone in boars by gas chromatography/mass spectrometry

17beta-Nortestosterone (17betaN) is illegally used in livestock as a growth promoter and its endogenous production has been described in some animals, such as adult boars. In this paper, the metabolism of 17betaN in boars has been studied by gas chromatography/mass spectrometry (GC/MS) in order to identify markers of the exogenous administration. Administration studies of intramuscular 17betaN laurate to male pigs were performed. Free, sulphate and glucuronide fractions of the urine samples were separated and the steroids present were quantified by GC/MS. 17betaN was detected in some pre-administration samples. After administration, 17betaN, norandrosterone, noretiocholanolone (NorE), norepiandrosterone, 5beta-estrane-3alpha,17beta-diol and 5alpha-estrane-3beta,17beta-diol were detected in different fractions, being the most important metabolites, 17betaN excreted as a sulphate and free NorE. Samples collected in routine controls were also analyzed by GC/MS to identify endogenous compounds. 17betaN, norandrostenedione and estrone were detected in almost all the samples. No other 17betaN metabolites were detected. According to these results, the detection by GC/MS of some of the 17betaN metabolites described above, different from 17betaN, could be indicative of the exogenous administration of 17betaN to boars.     

Desulfuration and Cyclization of (Z)‐2‐[Amino(pyridine‐2‐yl)methylene]‐ hydrazonecarbothioamide in the Presence of Manganese(II)

The reaction of (Z)‐2‐[amino(pyridine‐2‐yl)methylene]hydrazonecarbothioamide (HAm4DH) with Mn(ClO₄)₂·6H₂O afforded different mononuclear or polynuclear manganese(II) complexes, the nature of which apparently depended on the solvent used. For example, in ethanol a compound of formula [Mn(HAm4DH)₂](ClO₄)₂ ( 1 ) was obtained, where HAm4DH coordinates as a common tridentate NNS donor, but the [Mn(bpy)₂(NCS)₂] complex ( 2 ) (bpy = 2,2'‐bipyridine) has also been obtained – probably due to C–N bond cleavage of the thiosemicarbazone. Nevertheless, in a basic aqueous medium [Mn(bpy)₃](ClO₄)₂·0.5bpy ( 3 ) is formed and there is structural evidence for chemical transformations of the thiosemicarbazone promoted by Mn^II. Thus, the sulfate in {[Mn(py)₄Mn(py)₂(H₂O)₂(μ‐SO₄)₂]·4H₂O}_n ( 4 ) or sulfate and cyclooctasulfur in [Mn(pta)₂(pdo)]₄(SO₄)₂·4H₂O·S₈] ( 5 ), where pta is 3‐(pyridin‐2‐yl)‐1,2,4‐triazol‐5‐amine and pdo is (2R,4R/2S,4S)‐pentane‐2,4‐diolato, arise from the desulfuration and oxidation of the thiosemicarbazone ligand. The structures of complexes 2 to 5 were established by single‐crystal X‐ray diffraction. The formation of pta is the result of the oxidative cyclization of HAm4DH. In the polynuclear complex 4 , the sulfate acts as an (O,O') bridge between alternating Mn(py)₂(H₂O)₂ and Mn(py)₄ centers. In the tetranuclear complex 5 , pta acts as a bischelating ligand through the N‐pyridine and N‐triazole, and pdo act as a bridge between two manganese atoms. It is also noteworthy that in complexes 4 and 5 hydrogen bonds give rise to different self‐assembly behaviour that leads to complicated supramolecular structures.     

Transient dimer formation in supercritical carbon dioxide as seen from Raman scattering

The polarized and depolarized Raman profiles of supercritical CO(2) have been measured in the region of the nu(2) bending mode (forbidden transition at about 668 cm(-1)) and for the Fermi dyad (1285 and 1388 cm(-1)) along the isotherms 307, 309, 313, and 323 K in a reduced density domain 0.04相似文献   

Synthesis and biological evaluation of guanidine-type iminosugars

The preparation of carbohydrate mimics in which the endocyclic oxygen has been replaced by a guanidine-type nitrogen atom is reported. The synthetic strategy involves the furanose --> piperidine rearrangement of 5-deoxy-5-guanidino-L-idose precursors. The reaction proceeds through elimination of water to give 3-oxopiperidines, which were isolated as the corresponding hydrates. Biological evaluation of the new glycomimetics evidenced a strong influence of the nature of the substituents at the nitrogen atoms on the glycosidase inhibitory properties.     

Application of the Partial Least Square Technique to Identify Critical Variables in the Immunosorbent Manufacturing

The partial least square technique (PLS) was applied to the monoclonal antibody (Mab) CB.Hep-1 immunosorbent manufacturing to determine the influence of cyanate ester concentration, ligand concentration and target ligand density on Mab coupling efficiency, elution capacity, Hepatitis B surface antigen purity and ligand leakage (output variables). Results demonstrated that cyanate ester concentration, ligand concentration and density do not have an influence on output variables in assessed ranges. Conversely, the eluted antigen purity was significantly influenced by cyanate ester concentration and ligand concentration. In conclusion, the PLS application allows for the identification of critical variables and improvement of established chromatographic processes.     

Evidence for structural variants of a- and b-type peptide fragment ions using combined ion mobility/mass spectrometry

Tandem mass spectrometry (MS/MS) of peptides plays a key role in the field of proteomics, and an understanding of the fragmentation mechanisms involved is vital for data interpretation. Not all the fragment ions observed by low-energy collision-induced dissociation of protonated peptides are readily explained by the generally accepted structures for a- and b-ions. The possibility of a macrocyclic structure for b-type ions has been recently proposed. In this study, we have undertaken investigations of linear protonated YAGFL-NH(2), N-acetylated-YAGFL-NH(2), and cyclo-(YAGFL) peptides and their fragments using a combination of ion mobility (IM) separation and mass spectrometry. The use of IM in this work both gives insight into relative structural forms of the ion species and crucial separation of isobaric species. Our study provides compelling evidence for the formation of a stable macrocyclic structure for the b(5) ion generated by fragmentation of protonated linear YAGFL-NH(2). Additionally we demonstrate that the a(4) ion fragment of protonated YAGFL-NH(2) has at least two structures; one of which is attributable to a macrocyclic structure on the basis of its subsequent fragmentation. More generally, this work emphasizes the value of combined IM-MS/MS in probing the detailed fragmentation mechanisms of peptide ions, and illustrates the use of combined ion mobility/collisional activation/mass spectrometry analysis in achieving an effective enhancement of the resolution of the mobility separator.