Combining proton and phosphorus magnetic resonance spectroscopy offers a unique opportunity to study the oxidative and glycolytic components of metabolism in working muscle. This paper presents a 7 T proton calf coil design that combines dipole and loop elements to achieve the high performance necessary for detecting metabolites with low abundance and restricted visibility, specifically lactate, while including the option of adding a phosphorus array. We investigated the transmit, receive, and parallel imaging performance of three transceiver dipoles with six pair-wise overlap-decoupled standard or twisted pair receive-only coils. With a higher SNR and more efficient transmission decoupling, standard loops outperformed twisted pair coils. The dipoles with standard loops provided a four-fold-higher image SNR than a multinuclear reference coil comprising two proton channels and 32% more than a commercially available 28-channel proton knee coil. The setup enabled up to three-fold acceleration in the right-left direction, with acceptable g-factors and no visible aliasing artefacts. Spectroscopic phantom measurements revealed a higher spectral SNR for lactate with the developed setup than with either reference coil and fewer restrictions in voxel placement due to improved transmit homogeneity. This paper presents a new use case for dipoles and highlights their advantages for the integration in multinuclear calf coils.
- MeSH
- fantomy radiodiagnostické * MeSH
- kosterní svaly * diagnostické zobrazování chemie MeSH
- kyselina mléčná chemie metabolismus MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie metody MeSH
- magnetická rezonanční tomografie * metody MeSH
- poměr signál - šum MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
A film-forming system (FFS) represents a convenient topical dosage form for drug delivery. In this study, a non-commercial poly(lactic-co-glycolic acid) (PLGA) was chosen to formulate an FFS containing salicylic acid (SA) and methyl salicylate (MS). This unique combination is advantageous from a therapeutic point of view, as it enabled modified salicylate release. It is beneficial from a technological perspective too, because it improved thermal, rheological, and adhesive properties of the in situ film. DSC revealed complete dissolution of SA and good miscibility of MS with the polymer. MS also ensures optimal viscoelastic and adhesive properties of the film, leading to prolonged and sustained drug release. The hydrolysis of MS to active SA was very slow at skin pH 5.5, but it apparently occurred at physiological pH 7.4. The film structure is homogeneous without cracks, unlike some commercial preparations. The dissolution study of salicylates revealed different courses in their release and the influence of MS concentration in the film. The formulated PLGA-based FFS containing 5 % SA and 10 % MS is promising for sustained and prolonged local delivery of salicylates, used mainly for keratolytic and anti-inflammatory actions and pain relief.
- MeSH
- aplikace kožní MeSH
- aplikace lokální MeSH
- chemie farmaceutická metody MeSH
- koncentrace vodíkových iontů MeSH
- kopolymer kyseliny glykolové a mléčné * chemie MeSH
- kůže metabolismus MeSH
- kyselina mléčná * chemie MeSH
- kyselina polyglykolová * chemie MeSH
- kyselina salicylová * aplikace a dávkování chemie farmakokinetika MeSH
- léky s prodlouženým účinkem MeSH
- rozpustnost MeSH
- salicylany * aplikace a dávkování chemie farmakokinetika MeSH
- systémy cílené aplikace léků * metody MeSH
- uvolňování léčiv MeSH
- Publikační typ
- časopisecké články MeSH
Amine-containing drugs often show poor pharmacological properties, but these disadvantages can be overcome by using a prodrug approach involving self-immolative linkers. Accordingly, we designed l-lactate linkers as ideal candidates for amine delivery. Furthermore, we designed linkers bearing two different cargos (aniline and phenol) for preferential amine cargo release within 15 min. Since the linkers carrying secondary amine cargo showed high stability at physiological pH, we used our strategy to prepare phosphate-based prodrugs of the antibiotic Ciprofloxacin. Therefore, our study will facilitate the rational design of new and more effective drug delivery systems for amine-containing drugs.
- MeSH
- aminy chemie MeSH
- antibakteriální látky chemie MeSH
- ciprofloxacin chemie MeSH
- fosfáty chemie MeSH
- koncentrace vodíkových iontů MeSH
- kyselina mléčná chemie MeSH
- léčivé přípravky chemie MeSH
- prekurzory léčiv chemie MeSH
- systémy cílené aplikace léků metody MeSH
- Publikační typ
- časopisecké články MeSH
Strains of Limosilactobacillus reuteri are used as starter and bioprotective cultures and contribute to the preservation of food through the production of fermentation metabolites lactic and acetic acid, and of the antimicrobial reuterin. Reuterin consists of acrolein and 3-hydroxypropionaldehyde (3-HPA), which can be further metabolized to 1,3-propanediol and 3-hydroxypropionic acid (3-HP). While reuterin has been the focus of many investigations, the contribution of 3-HP to the antimicrobial activity of food related reuterin-producers is unknown. We show that the antibacterial activity of 3-HP was stronger at pH 4.8 compared to pH 5.5 and 6.6. Gram-positive bacteria were in general more resistant against 3-HP and propionic acid than Gram-negative indicator strains including common food pathogens, while spoilage yeast and molds were not inhibited by ≤ 640 mM 3-HP. The presence of acrolein decreased the minimal inhibitory activity of 3-HP against E. coli indicating synergistic antibacterial activity. 3-HP was formed during the growth of the reuterin-producers, and by resting cells of L. reuteri DSM 20016. Taken together, this study shows that food-related reuterin producers strains synthesize a second antibacterial compound, which might be of relevance when strains are added as starter or bioprotective cultures to food products.
- MeSH
- antiinfekční látky chemie metabolismus farmakologie MeSH
- Bacteria účinky léků růst a vývoj MeSH
- fermentace MeSH
- glyceraldehyd analogy a deriváty chemie metabolismus MeSH
- glycerol metabolismus MeSH
- koncentrace vodíkových iontů MeSH
- kyselina mléčná analogy a deriváty chemie metabolismus farmakologie MeSH
- kyselina octová metabolismus MeSH
- Lactobacillaceae chemie růst a vývoj metabolismus MeSH
- potravinářská mikrobiologie MeSH
- propan chemie metabolismus MeSH
- stabilita léku MeSH
- Publikační typ
- časopisecké články MeSH
Two enantiomers of lactic acid exist. While L-lactic acid is a common compound of human metabolism, D-lactic acid is produced by some strains of microorganism or by some less relevant metabolic pathways. While L-lactic acid is an endogenous compound, D-lactic acid is a harmful enantiomer. Exposure to D-lactic acid can happen by various ways including contaminated food and beverages and by microbiota during some pathological states like short bowel syndrome. The exposure to D-lactic acid cannot be diagnosed because the common analytical methods are not suitable for distinguishing between the two enantiomers. In this review, pathways for D-lactic acid, pathological processes, and diagnostical and analytical methods are introduced followed by figures and tables. The current literature is summarized and discussed.
Liquid crystals (LCs) are among the most prominent materials of the current information age, mainly due to their well-known application in liquid crystal displays (LCDs). Their unique electro-optical properties stem from their ability to form organised structures (mesophases) on the transition from solid state to isotropic liquid. Molecules of LCs in a mesophase still maintain the anisotropy of solid crystals, while simultaneously exhibiting the fluidity of liquids, which gives the system the ability to react immediately to external stimuli such as electric or magnetic fields, light, mechanical stress, pressure and, of course, temperature. For the proper function of LC-based devices, not only chemical, but also optical purity of materials is strongly desirable, since any impurity could be detrimental to the self-assembly of the molecules. Therefore, in this study we aimed to verify synthetic methods published in the literature, which are used nowadays to prepare chiral building blocks based on lactic acid, for their enantioselectivity. Moreover, we have focused on the development of an analytical chiral separation method for target liquid crystalline materials. Using a chiral polysaccharide-based column operated in liquid chromatography mode, we show that not all published methods of LC synthesis are enantioselective, which could lead to significant differences in the properties of the resulting materials. We show that high-performance liquid chromatography with UV detection and supercritical fluid chromatography with UV and mass spectrometry detection enable full control over the chemical and optical purity of the target LCs and the corresponding chiral building blocks. For the first time, we utilise supercritical fluid chromatography with mass detection for the direct chiral analysis of liquid crystalline materials and impurities formed during the synthesis.
A new method for the preparation of anhydrous ethyl ester of lactic acid was studied. The selected method is based on catalytic transesterification of lactic acid oligomers, which were prepared for this purpose by autocatalytic oligomerization of lactic acid. In this work, a kinetic model for the case of catalytic alcoholysis of oligoesters was derived assuming a first-order reaction and equimolar content of reactants in the reaction mixture. The model makes it possible to obtain the values of the reaction rate and equilibrium constants and the equilibrium alcohol concentration by regression analysis at one time. The model was verified by measuring the rate of consumption of ethanol over the time at various reaction temperatures with anhydrous FeCl₃ as the catalyst. The reaction was studied at overpressure under autogenous conditions in the temperature range of 100⁻180 °C. For the catalyst concentration of 1 mol %, the activation energy value was 64.35 kJ·mol-1. The dependence of equilibrium composition and rate constant on the temperature was obtained. The derived model is generally applicable to all first-order equilibrium reactions. The presumption is that the forward and reverse reactions are of the same order and have the same stoichiometry and equivalent amounts of reactants at the beginning of the reaction.
Drug access to the CNS is hindered by the presence of the blood-brain barrier (BBB), and the intranasal route has risen as a non-invasive route to transport drugs directly from nose-to-brain avoiding the BBB. In addition, nanoparticles (NPs) have been described as efficient shuttles for direct nose-to-brain delivery of drugs. Nevertheless, there are few studies describing NP nose-to-brain transport. Thus, the aim of this work was (i) to develop, characterize and validate in vitro olfactory cell monolayers and (ii) to study the transport of polymeric- and lipid-based NPs across these monolayers in order to estimate NP access into the brain using cell penetrating peptide (CPPs) moieties: Tat and Penetratin (Pen). All tested poly(d,l-lactide-co-glycolide) (PLGA) and nanostructured lipid carrier (NLC) formulations were stable in transport buffer and biocompatible with the olfactory mucosa cells. Nevertheless, 0.7% of PLGA NPs was able to cross the olfactory cell monolayers, whereas 8% and 22% of NLC and chitosan-coated NLC (CS-NLC) were transported across them, respectively. Moreover, the incorporation of CPPs to NLC surface significantly increased their transport, reaching 46% of transported NPs. We conclude that CPP-CS-NLC represent a promising brain shuttle via nose-to-brain for drug delivery.
- MeSH
- aplikace intranazální MeSH
- biologický transport MeSH
- chemie farmaceutická metody MeSH
- chitosan chemie MeSH
- čichová sliznice cytologie metabolismus MeSH
- hematoencefalická bariéra metabolismus MeSH
- krysa rodu rattus MeSH
- kyselina mléčná chemie MeSH
- kyselina polyglykolová chemie MeSH
- lipidy chemie MeSH
- mozek metabolismus MeSH
- nanočástice * MeSH
- nos MeSH
- nosní sliznice metabolismus MeSH
- penetrační peptidy chemie MeSH
- polymery chemie MeSH
- potkani Wistar MeSH
- systémy cílené aplikace léků * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- validační studie MeSH
The aim of the study was to prepare PLGA microparticles for prolonged release of mirtazapine by o/w solvent evaporation method and to evaluate effects of PVA concentration and organic solvent choice on microparticles characteristics (encapsulation efficiency, drug loading, burst effect, microparticle morphology). Also in vitro drug release tests were performed and the results were correlated with kinetic model equations to approximate drug release mechanism. It was found that dichloromethane provided microparticles with better qualities (encapsulation efficiency 64.2%, yield 79.7%). Interaction between organic solvent effect and effect of PVA concentration was revealed. The prepared samples released the drug for 5 days with kinetics very close to that of zero order (R(2 )= 0.9549 - 0.9816). According to the correlations, the drug was probably released by a combination of diffusion and surface erosion, enhanced by polymer swelling and chain relaxation.
- MeSH
- antidepresiva chemie MeSH
- kinetika MeSH
- kyselina mléčná chemie MeSH
- kyselina polyglykolová chemie MeSH
- léky s prodlouženým účinkem chemie MeSH
- methylenchlorid chemie MeSH
- mianserin analogy a deriváty chemie MeSH
- mikrosféry MeSH
- rozpouštědla chemie MeSH
- uvolňování léčiv MeSH
- Publikační typ
- časopisecké články MeSH
Commercially available antibacterial semisolid preparations intended for topical application provide only short-term drug release. A sustained kinetics is possible by exploitation of a biodegradable polymer carrier. The purpose of this work is to formulate a mucoadhesive system with aciclovir (ACV) based on a solid molecular dispersion of this drug in poly(lactic-co-glycolic acid) branched on tripenterythritol (PLGA/T). The ACV incorporation into PLGA/T was carried out either by solvent method, or melting method, or plasticization method using various plasticizers. The drug-polymer miscibility, plasticizer efficiency and content of residual solvent were found out employing DSC. Viscosity was measured at the shear rate range from 0.10 to 10.00 s(-1) at three temperatures and data were analyzed by Newtonian model. The mucoadhesive properties were ascertained in the tensile test on a mucin substrate. The amount of ACV released was carried out in a wash-off dissolution test. The DSC results indicate a transformation of crystalline form of ACV into an amorphous dissolved in branched polyester carrier, and absence of methyl formate residuals in formulation. All the tested plasticizers are efficient at Tg depression and viscosity decrease. The non-conventional ethyl pyruvate possessing supportive anti-inflammatory activity was evaluated as the most suitable plasticizer. The ACV release was strongly dependent on the ethyl pyruvate concentration and lasted from 1 to 10 days. The formulated PLGA/T system with ACV exhibits increased adhesion to mucosal hydrophilic surfaces and prolonged ACV release controllable by degradation process and viscosity parameters.
- MeSH
- acyklovir aplikace a dávkování chemie MeSH
- biokompatibilní materiály chemie MeSH
- časové faktory MeSH
- hydrofobní a hydrofilní interakce MeSH
- kyselina mléčná chemie MeSH
- kyselina polyglykolová chemie MeSH
- léky s prodlouženým účinkem MeSH
- povrchové vlastnosti MeSH
- uvolňování léčiv MeSH
- velikost částic MeSH
- zvláčňovadla aplikace a dávkování chemie MeSH
- Publikační typ
- časopisecké články MeSH
