A low-pressure liquid chromatography system for the on-line quantification of caffeine loaded into lipid nanoparticles that permeates pig skin was developed. The apparatus includes a Franz diffusion cell with computer-controlled sampling that allows collection of acceptor solution with automatic compensation for sample withdrawing, and a C-18 reversed-phase monolithic column integrated in a typical Flow Injection Analysis (FIA) set-up where separation between caffeine and other matrix elements is performed before spectrophotometric quantification at 273 nm. Several parameters regarding chromatographic analysis (propulsion element, column length, mobile phase composition, and flow rate) were studied along with the establishment of the sampling procedure. Under the selected conditions (monolithic column Chromolith® RP-18 15 mm × 4.6 mm i.d., acetonitrile:water 10:90 (v/v), flow rate 0.45 mL min(-1)) a detection limit of 4 μM and RSD values for caffeine concentration <2% were achieved. High recovery values were obtained when Hepes buffer incubated as acceptor solution in presence of pig skin for 8 h was spiked with caffeine (103±5%). The developed system also accounts for low organic solvent consumption, low operating costs, low generation of waste and high sample throughput (24 h(-1)). Due to the real time automated sampling and high throughput, transdermal permeation profiles of nanoformulations can be established within a time frame seldom observed by conventional techniques.

• MeSH
• automatizace MeSH
• chromatografie s reverzní fází metody   MeSH
• difuze MeSH
• kofein analýza   chemie   MeSH
• kůže metabolismus   MeSH
• lidé MeSH
• limita detekce MeSH
• lipidy chemie   MeSH
• nanočástice chemie   MeSH
• nosiče léků chemie   metabolismus   MeSH
• permeabilita MeSH
• prasata MeSH
• průtoková injekční analýza MeSH
• reprodukovatelnost výsledků MeSH
• tlak * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• fluorescenční spektrometrie využití   MeSH
• kyselina salicylová analýza   MeSH
• léčivé přípravky analýza   MeSH
• masti analýza   aplikace a dávkování   MeSH
• průtoková injekční analýza metody   MeSH
• techniky in vitro MeSH

The assessment of percutaneous absorption of molecules is a very important step in the evaluation of any dermal or transdermal drug delivery system. In order to perform percutaneous drug absorption studies, it is essential that the methods are standardized and that the integrity of the skin is monitored and maintained to ensure that the data obtained are valid and relevant. Reproducible data on percutaneous absorption in humans are as well required to predict the systemic risk from dermal exposure to chemicals, such as hazardous substances at the workplace, agrochemicals and cosmetic ingredients. In vitro and animal models provide important tools for screening a series of drug formulations, evaluation of skin permeation enhancing properties and mechanism of action of the carrier systems and estimation of rank of skin transport for a series of drug molecules. In this review, we have summarized in vitro testing of skin absorption using static Franz-type diffusion cells.

• MeSH
• farmaceutická chemie MeSH
• kožní absorpce MeSH
• kůže metabolismus   MeSH
• léčivé přípravky metabolismus   MeSH
• lidé MeSH
• modely u zvířat MeSH
• nosiče léků chemie   MeSH
• permeabilita MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Misuse of various chemicals, such as chemical warfare agents, industrial chemicals or pesticides during warfare or terrorists attacks requires adequate protection. Thus, development and evaluation of novel decontamination dispositives and techniques are needed. In this study, in vitro permeation and decontamination of a potentially hazardous compound paraoxon, an active metabolite of organophosphorus pesticide parathion, was investigated. Skin permeation and decontamination experiments were carried out in modified Franz diffusion cells. Pig skin was used as a human skin model. Commercially produced detergent-based washing solutions FloraFree(™) and ArgosTM were used as decontamination means. The experiments were done under "warm", "cold", "dry" and "wet" skin conditions in order to determine an effect of various physical conditions on skin permeation of paraoxon and on a subsequent decontamination process. There was no significant difference in skin permeation of paraoxon under warm, cold and dry conditions, whereas wet conditions provided significantly higher permeation rates. In the selected conditions, decontamination treatments performed 1 h after a skin exposure did not decrease the agent volume that permeated through the skin. An exception were wet skin conditions with non-significant decontamination efficacy 18 and 28% for the FloraFree(™) and Argos(™) treatment, respectively. In contrast, the skin permeation of paraoxon under warm, cold and dry conditions increased up to 60-290% following decontamination compared to non-decontaminated controls. This has previously been described as a skin wash-in effect.

• MeSH
• časové faktory MeSH
• chemické jevy MeSH
• dekontaminace * metody   MeSH
• detergenty farmakologie   MeSH
• difuzní komory kultivační MeSH
• kožní absorpce účinky léků   fyziologie   MeSH
• kůže chemie   účinky léků   metabolismus   MeSH
• lidé MeSH
• paraoxon chemie   farmakokinetika   MeSH
• permeabilita účinky léků   MeSH
• pesticidy chemie   farmakokinetika   MeSH
• Sus scrofa MeSH
• techniky in vitro MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Transdermal administration of drugs that penetrate, in this case directly into the blood circulation, has many advantages and is promising for many drugs thanks to its easy application and good patient compliance. (S)-8-Methyl-6,9-diazaspiro[4.5]decan-7,10-dione (alaptide), has been studied as a potential chemical permeation enhancer. Based on its structure, four selected piperazine-2,5-diones were synthesized by means of multi-step synthetic pathways. All the compounds were investigated on their ability to enhance the permeation of the model drug theophylline from the hydrophilic medium propylene glycol:water (1:1). In vitro experiments were performed using vertical Franz diffusion cells at constant temperature 34 ± 0.5 °C and using full-thickness pig (Sus scrofa f. domestica) ear skin. Withdrawn samples were analyzed by RP-HPLC for determination of the permeated amount of theophylline. All the compounds were applied in ratio 1:10 (w/w) relative to the amount of theophylline. One hour after application, the permeated amount of theophylline from formulations with alaptide and (3S,6S)-3,6-dimethylpiperazine-2,5-dione, was ca. 15- and 12-fold higher, respectively, than from the formulation without the tested compounds. Despite the enhancement ratio of both enhancers in a steady state was ca. 2.3, the pseudo-enhancement ratio in the time range from 1 to 3 h was 4.4. These enhancement ratios indicate that the compounds are able to enhance the permeation of agents through the skin; however, the short-term application of both compound formulations seems to be more advantageous. In addition, the screening of the cytotoxicity of all the prepared compounds was performed using three cell lines, and the compounds did not show any significant toxic effect.

• MeSH
• kožní absorpce * MeSH
• lidé MeSH
• molekulární struktura MeSH
• nádorové buněčné linie MeSH
• permeabilita MeSH
• piperazin chemie   farmakokinetika   MeSH
• theofylin chemie   farmakokinetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The main objective of the current research work was to synthesize mesoporous silica nanoparticles for controlled delivery of mometasone furoate for potential nasal delivery. The optimized sol-gel method was used for the synthesis of mesoporous silica nanoparticles. Synthesized nanoparticles were processed through Zeta sizer, SEM, TEM, FTIR, TGA, DSC, XRD, and BET analysis for structural characterization. The in vitro dissolution test was performed for the inclusion compound, while the Franz diffusion experiment was performed for permeability of formulation. For the determination of expression levels of anti-inflammatory cytokines IL-4 and IL-5, RNA extraction, reverse transcription, and polymerase chain reaction (RT-PCR) were performed. The MTT assay was also performed to determine cell viability. Synthesized and functionalized mesoporous silica nanoparticles showed controlled release of drugs. FT-IR spectroscopy confirmed the presence of the corresponding functional groups of drugs within mesoporous silica nanoparticles. Zeta sizer and thermal analysis confirmed the delivery system was in nano size and thermally stable. Moreover, a highly porous system was observed during SEM and TEM evaluation, and further it was confirmed by BET analysis. Greater cellular uptake with improved permeability characteristics was also observed. As compared to the crystalline drug, a significant improvement in the dissolution rate was observed. It was concluded that stable mesoporous silica nanoparticles with significant porosity were synthesized, efficiently delivering the loaded drug without any toxic effect.

• Publikační typ
• časopisecké články MeSH

Drug compounds including memantine moieties are an important group of biologically active agents for different pathologies, including the Alzheimer's disease. In the present study, a series of memantine derivatives incorporating amino acid residues have been synthesized and their neuroprotective in vitro evaluation in respect of the Alzheimer's disease, involving the effects on the resistance to Aβ toxicity, excitotoxicity, oxidative stress, hypoxia, and neuroinflammation has been studied. The cytotoxicities of the compounds were detected by CPE assay. TC50 and IC50 were determined using Reed and Muench method. Solubility and distribution were measured using a shake-flask method. Permeability of the compounds was studied using Franz diffusion cell and Permeapad™ barrier. These compounds displayed apparent multi-neuroprotective effects against copper-triggered Aβ toxicity, glutamate-induced excitotoxicity, and oxidative and hypoxic injuries. They also showed the ability to inhibit the inflammatory cytokine release from the activated microglia and potential anti-neuroinflammatory effects. Especially, two most promising compounds H-4-F-Phe-memantine and H-Tyr-memantine demonstrated the equivalent functional bioactivities in comparison with the positive control memantine hydrochloride. Higher solubility in muriatic buffer than in phosphate buffer was detected. The distribution coefficients showed the optimal lipophilicity for compounds. The presented results propose new class of memantine derivatives as potential drug compounds. Based on the experimental results, the correlations have been obtained between the biological, physicochemical parameters and structural descriptors. The correlation equations have been proposed to predict the properties of new memantine derivatives knowing only the structural formula.

• MeSH
• Alzheimerova nemoc farmakoterapie   genetika   patologie   MeSH
• amyloidní beta-protein účinky léků   toxicita   MeSH
• buňky MDCK MeSH
• chřipka lidská farmakoterapie   virologie   MeSH
• kyselina glutamová metabolismus   MeSH
• lidé MeSH
• memantin analogy a deriváty   chemie   farmakologie   MeSH
• neuroprotektivní látky chemie   farmakologie   MeSH
• Orthomyxoviridae účinky léků   patogenita   MeSH
• oxidační stres účinky léků   MeSH
• psi MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

A simple HPLC/UV method for the determination of the transdermal permeation and dermal penetration of a broad-spectrum antiviral drug adefovir (PMEA) was developed. The separation was achieved on a C18 column with the mobile phase composed of 10 mM KH2PO4 and 2 mM Bu4NHSO4 at pH 6.0 and 7% acetonitrile. The method was validated with respect to selectivity, linearity (0.1-50 microg/ml), precision, accuracy, and stability. Transdermal permeation of 2% PMEA was studied in vitro using the Franz diffusion cell and porcine skin. The flux values were 1.8, 3.0, and 0.6 microg/cm2/h from aqueous donor samples at pH 3.4 and 7.4, and isopropyl myristate, respectively. The respective skin concentrations at 48 h were 294, 263, and 971 microg/g from these vehicles. These results will serve as a lead for further studies on transdermal and topical delivery of antivirals from the group of acyclic nucleoside phosphonates.

• MeSH
• adenin analogy a deriváty   analýza   aplikace a dávkování   MeSH
• antivirové látky analýza   aplikace a dávkování   farmakokinetika   MeSH
• aplikace kožní MeSH
• financování organizované MeSH
• kožní absorpce MeSH
• kůže metabolismus   MeSH
• organofosfonáty analýza   aplikace a dávkování   farmakokinetika   MeSH
• prasata MeSH
• reprodukovatelnost výsledků MeSH
• spektrofotometrie ultrafialová metody   MeSH
• techniky in vitro MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH

Dermal absorption of the herbicide chlorotoluron was measured using ex vivo pig skin in Franz diffusion cells in an automated system. The steady-state flux was calculated, as well as the permeability coefficient, which is 0.0038 cm h(-1). The permeability coefficient (Kp) is a key factor when predicting human health risks resulting from dermal exposition to a substance. The experimental determination of this parameter filled data gaps regarding the dermal absorption of chlorotoluron. The experimental permeability coefficient was subsequently used to calculate the dermal absorbed dose during some exposure scenarios. Reference doses were revised, and screening risk assessment process was done to calculate the risks resulting from exposure to chlorotoluron. This refined new approach proved to be a useful tool for human health risk assessment in the areas with these herbicide applications. Graphical Abstract An experimentally refined tool to assess the risks of the human dermal exposure to herbicide chlorotoluron.

• MeSH
• fenylmočovinové sloučeniny metabolismus   toxicita   MeSH
• herbicidy metabolismus   toxicita   MeSH
• hodnocení rizik MeSH
• kožní absorpce MeSH
• kůže metabolismus   MeSH
• lidé MeSH
• permeabilita MeSH
• Sus scrofa MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The objective of this work was to investigate feasibility of transdermal and dermal delivery of adefovir (9-(2-phosphonomethoxyethyl)adenine), a broad-spectrum antiviral from the class of acyclic nucleoside phosphonates. Transport of 2% adefovir through and into porcine skin and effects of various solvents, pH, and permeation enhancers were studied in vitro using Franz diffusion cell. From aqueous donor samples, adefovir flux through the skin was 0.2-5.4 microg/cm2/h with greatest permeation rate at pH 7.8. The corresponding adefovir skin concentrations reached values of 120-350 microg/g of tissue. Increased solvent lipophilicity resulted in higher skin concentration but had only minor effect on adefovir flux. A significant influence of counter ions on both transdermal and dermal transport of adefovir zwitterion was observed at pH 3.4. Permeation enhancer dodecanol was ineffective, 1-dodecylazepan-2-one (Azone) and dodecyl 2-(dimethylamino)propionate (DDAIP) showed moderate activity. The highest adefovir flux (11.3+/-3.6 microg/cm2/h) and skin concentration (1549+/-416 microg/g) were achieved with 1% Transkarbam 12 (5-(dodecyloxycarbonyl)pentylammonium 5-(dodecyloxycarbonyl)pentylcarbamate) at pH 4. This study suggests that, despite its hydrophilic and ionizable nature, adefovir can be successfully delivered through the skin.

• MeSH
• adenin analogy a deriváty   aplikace a dávkování   farmakokinetika   MeSH
• antivirové látky aplikace a dávkování   farmakokinetika   MeSH
• aplikace kožní MeSH
• financování organizované MeSH
• koncentrace vodíkových iontů MeSH
• kožní absorpce účinky léků   MeSH
• lékové transportní systémy MeSH
• lidé MeSH
• organofosfonáty aplikace a dávkování   farmakokinetika   MeSH
• permeabilita MeSH
• pomocné látky MeSH
• rozpouštědla MeSH
• techniky in vitro MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Check Tag
• lidé MeSH