Electronic structure modifications induced by increased molecular complexity: from triphenylamine to m-MTDATA.

The starburst π-conjugated molecule 4,4',4''-tris(N-3-methylphenyl-N-phenyl-amino)triphenylamine (C57H48N4, m-MTDATA), based on triphenylamine (TPA) building blocks, is widely used in optoelectronic devices due to its good electron-donor characteristics. The electronic structure of m-MTDATA was investigated for the first time in the gas phase by means of PhotoElectron Spectroscopy (PES) and Near Edge X-ray Absorption Fine Structure (NEXAFS) spectroscopy. The combination of Density Functional Theory (DFT) calculations with the experimental spectra provides a comprehensive description of the molecular electronic structure. Moreover, by comparing the results with previous TPA measurements, we could shed light on how the electronic structure evolves when the molecular size is increased. We found that the C 1s photoelectron spectra of m-MTDATA and TPA are similar, due to the balance of the counter-acting effects of the electronegativity of the N atoms and the delocalization of the amine lone-pair electrons. In contrast, the increased number of N atoms (i.e. N lone pairs) in m-MTDATA determines a three-peak feature in the outermost valence binding energy region with strong contributions by the N 2pz orbitals. We also obtained a decrease of the HOMO-LUMO gap for m-MTDATA, which points to improved electron donating properties of m-MTDATA with respect to TPA.

Electronic Structure Characterization of a Thiophene Benzo-Annulated Series of Common Building Blocks for Donor and Acceptor Compounds Studied by Gas Phase Photoelectron and Photoabsorption Synchrotron Spectroscopies.

The near-edge x-ray-absorption fine-structure (NEXAFS) and X-ray photoelectron spectroscopy (XPS) spectra of benzo[ b]thiophene (BBT) and dibenzothiophene (DBT) in the gas phase have been measured at the carbon K-edge and sulfur LII,III-edge regions. The assignment of the spectral features has been provided by theoretical calculations based on density functional theory (DFT) and its time-dependent generalization (TDDFT) in the linear response regime. Observed trends in computed C 1s and S 2p ionization potentials (IPs) have been rationalized in terms of both the inductive effects due to the presence of S and the increased π-electrons delocalization arising from the benzo-annulation process. The analysis of the NEXAFS carbon K-edge and sulfur LII,III-edge regions provided information on both low-lying delocalized virtual π orbitals, and higher-lying localized σ*(C-S) states. The evolution of the NEXAFS carbon K-edge spectral features along the series thiophene (T) and derivatives, BBT and DBT, is informative of a stabilizing effect due to increased aromaticity. This effect is however more pronounced in going from T to BBT compared to the introduction of a second annulated phenyl ring in DBT. The nature of the most intense sulfur LII,III-edge NEXAFS spectral features is instead conserved along the series reflecting thus the localized nature of the virtual states involved in the S 2p core-excitation process.

Electronic structure investigation of biphenylene films.

Photoelectron Spectroscopy (PS) and Near-Edge X-ray Absorption Fine Structure (NEXAFS) spectroscopy have been used to investigate the occupied and empty density of states of biphenylene films of different thicknesses, deposited onto a Cu(111) crystal. The obtained results have been compared to previous gas phase spectra and single molecule Density Functional Theory (DFT) calculations to get insights into the possible modification of the molecular electronic structure in the film induced by the adsorption on a surface. Furthermore, NEXAFS measurements allowed characterizing the variation of the molecular arrangement with the film thickness and helped to clarify the substrate-molecule interaction.

Experimental and theoretical study of electronic structure of lutetium bi-phthalocyanine.

Using Near Edge X-Ray Absorption Fine Structure (NEXAFS) Spectroscopy, the thickness dependent formation of Lutetium Phthalocyanine (LuPc2) films on a stepped passivated Si(100)2×1 reconstructed surface was studied. Density functional theory (DFT) calculations were employed to gain detailed insights into the electronic structure. Photoelectron spectroscopy measurements have not revealed any noticeable interaction of LuPc2 with the H-passivated Si surface. The presented study can be considered to give a comprehensive description of the LuPc2 molecular electronic structure. The DFT calculations reveal the interaction of the two molecular rings with each other and with the metallic center forming new kinds of orbitals in between the phthalocyanine rings, which allows to better understand the experimentally obtained NEXAFS results.

Potassium-intercalated H2Pc films: alkali-induced electronic and geometrical modifications.

X-ray spectroscopy studies of potassium intercalated metal-free phthalocyanine multilayers adsorbed on Al(110) have been undertaken. Photoelectron spectroscopy measurements show the presence of several charge states of the molecules upon K intercalation, due to a charge transfer from the alkali. In addition, the comparison of valence band photoemission spectra with the density functional theory calculations of the density of states of the H(2)Pc(-) anion indicates a filling of the formerly lowest unoccupied molecular orbital by charge transfer from the alkali. This is further confirmed by x-ray absorption spectroscopy (XAS) studies, which show a decreased density of unoccupied states. XAS measurements in different experimental geometries reveal that the molecules in the pristine film are standing upright on the surface or are only slightly tilted away from the surface normal but upon K intercalation, the molecular orientation is changed in that the tilt angle of the molecules increases.

Dual-drugs delivery in solid lipid nanoparticles for the treatment of Candida albicans mycosis.

Nowadays, a combinatorial drug delivery system that simultaneously transports two or more drugs to the targeted site in a human body, also recognized as a dual-drugs delivery system, represents a promising strategy to overcome drug resistance. Solid lipid nanoparticles loaded with clotrimazole (CLZ) and alphalipolic acid (ALA), considered as an effective agent in the reduction of reactive oxygen species, can enhance anti-infective immunity being proposed as a non-toxic and mainly non-allergic dual-drugs delivery system. In this study, uncoated and cationic CLZ-ALA-loaded SLN were prepared and compared. Suspensions with a narrow size distribution of particles of mean size below 150 nm were obtained, having slight negative or highly positive zeta potential values, due to the presence of the cationic lipid, which also increased nanoparticles stability, as confirmed by Turbiscan® results. Calorimetric studies confirmed the rationale of separately delivering the two drugs in a dual-delivery system. Furthermore, they confirmed the formation of SLN, without significant variation in presence of the cationic lipid. In vitro release studies showed a prolonged drug release without the occurrence of any burst effect. In vitro studies performed on 25 strains of Candida albicans showed the antimicrobial drug activity was not altered when it was loaded into lipid nanoparticles. The study has proved the successfully encapsulation of CLZ and ALA in solid lipid nanoparticles that may represent a promising strategy to combine ALA protective effect in the treatment with CLZ.

Effect of hyaluronic acid and polysaccharides from Opuntia ficus indica (L.) cladodes on the metabolism of human chondrocyte cultures.

Conventional medications in articular disease are often effective for symptom relief, but they can also cause significant side effects and do not slow the progression of the disease. Several natural substances have been shown to be effective as non-steroidal anti-inflammatory drugs at relieving the symptoms of osteoarthritis (OA), and preliminary evidence suggests that some of these compounds may exert a favourable influence on the course of the disease. In this study, we assay the anti-inflammatory/chondroprotective effect of some lyophilised extracts obtained from Opuntia ficus indica (L.) cladodes and of hyaluronic acid (HA) on the production of key molecules released during chronic inflammatory events such as nitric oxide (NO), glycosaminoglycans (GAGs), prostaglandins (PGE(2)) and reactive oxygen species (ROS) in human chondrocyte culture, stimulated with proinflammatory cytokine interleukin-1 beta (IL-1 beta). Further the antioxidant effect of these extracts was evaluated in vitro employing the bleaching of the stable 1,1-diphenyl-2-picrylhydrazyl radical (DPPH test). All the extracts tested in this study showed an interesting profile in active compounds. Particularly some of these extracts were characterized by polyphenolic and polysaccharidic species. In vitro results pointed out that the extracts of Opuntia ficus indica cladodes were able to contrast the harmful effects of IL-1 beta. Our data showed the protective effect of the extracts of Opuntia ficus indica cladodes in cartilage alteration, which appears greater than that elicited by hyaluronic acid (HA) commonly employed as visco-supplementation in the treatment of joint diseases.

Protective effect of Capparis spinosa on chondrocytes.

The aim of the present study was to evaluate the in vitro chondroprotective effects of the lyophilised methanolic extract from flowering buds of Capparis Spinosa L (LECS). This plant, common to the Mediterranean basin, has been used by the traditional medicine for its diuretic and antihypertensive effects and also in certain pathological conditions related to uncontrolled lipid peroxidation. The extract contains many constituents, in particular some flavonoids (kaempferol and quercetin derivatives) and hydrocinammic acids with several known biological effects such as the anti-inflammatory and the antioxidant ones. In this study, we assayed the effect of LECS on human chondrocytes cultures stimulated by proinflammatory cytokine interleukin-1beta (IL-1beta) and we determined the production of key molecules released during chronic inflammatory events (nitric oxide, glycosaminoglycans, prostaglandins and reactive oxygen species). We observed that LECS was able to counteract the harmful effects induced by IL-1beta. This protection appeared to be greater than that elicited by indomethacin, which is usually employed in joint diseases. Since LECS possess a chondroprotective effect, it might be used in the management of cartilage damage during the inflammatory processes.

Acute metabolic response to cold exposure in unipolar and bipolar II patients.

The thermoregulatory response to cold exposure was examined in 11 unipolar and 5 bipolar II drug-free outpatients and 12 healthy controls. Subjects were studied in an environmental chamber at 10 C for 60 min. The heat production response was derived from the rate of oxygen consumption measured at 15-min intervals. Rectal and mean skin temperatures were continuously recorded from thermistor probes. Responses of the controls were used to establish a standard range against which the responses of the patients were compared. Six unipolar patients (54.5%) fell outside the standard range (chi 2 = 8.86, df = 1, p less than 0.005). Four of these patients showed a paradoxical decrease in heat production. Responses of the bipolar II patients fell within a narrow segment of the standard range, such that 10 of 12 controls (83.3%) responded outside the segment (chi 2 = 10.12, df = 1, p less than 0.005). These findings indicate that unipolar patients show greater variability and bipolar II patients less variability than controls in thermoregulatory response to cold. These observations extend previous suggestions of hypothalamic-limbic system dysfunction in patients with depression.

Inhibition of cellular antioxidants: a possible mechanism of toxic cell injury.

Cells that utilize molecular oxygen generate highly reactive oxygen-derived free radicals. Endogenous cellular oxidants inactivate oxidant free radicals and protect aerobic cells from oxidant injury. Glutathione, glutathione reductase, and superoxide dismutase are key components of this antioxidant defense. Inhibition of antioxidant components would be expected to result in cell injury. Using exposure to oxygen at high pressure to increase the level of oxidant free radicals, evidence is presented to support the hypothesis that inhibition of cellular antioxidants renders organisms more susceptible to oxygen toxicity. Diethyldithiocarbamate at doses of 250, 500 and 1000 mg/kg inhibited rat brain superoxide dismutase activity and shortened onset time to seizures in a dose-related manner in 4 ATA oxygen. Carmustine at doses of 12.5, 25 and 50 mg/kg inhibits glutathione reductase activity in rat brain in proportion to the dose. Time to onset of seizures of rats pretreated with carmustine prior to exposure to 4 ATA oxygen was shortened, and oxidized glutathione levels were increased in the cortex and subcortex. These data suggest that inhibition of antioxidant components results in organisms becoming more sensitive to oxygen toxicity. Compounds that inhibit cellular antioxidants may produce toxic cell injury by permitting intracellular oxidant free radicals to attack essential cell constituents.

Nitrous oxide anesthesia in patients with ischemic chest discomfort: effect on beta-endorphins.

Relief of discomfort during acute myocardial ischemia is usually accomplished with a narcotic analgesic. Because these medications may cause unpleasant symptoms and exert a possibly adverse hemodynamic effect, the availability of alternative analgesic medication would be advantageous. Nitrous oxide is a commonly used potent analgesic gas. Nitrous oxide has been used to relieve ischemic discomfort during myocardial infarction. The current study was undertaken to corroborate that data in a randomized, blinded, cross-over study and to begin to explore a mechanism for the analgesic effect. Twelve patients with typical ischemic chest discomfort and a suspected myocardial infarction were included in the study. Each patient received a 30-minute inhalation treatment of 30% nitrous oxide/70% oxygen and 30 minutes of 30% room air/70% oxygen. Patients were blinded to their treatment and were randomized to receive nitrous oxide first, then room air, or vice versa. A semiquantitative assessment of the severity of chest discomfort was made before, during, and at the conclusion of each treatment together with a measurement of plasma beta-endorphin levels using a venous blood sample. Eleven of the 12 patients reported a significant reduction in the intensity of their chest discomfort during the nitrous oxide inhalation, but none had pain relief during the control period. Beta-endorphin levels fell to a greater extent during the inhalation of nitrous oxide than during the control period (51% versus 26%; P less than .05). No significant adverse effects were noted and most patients slept during the nitrous oxide inhalation. It is concluded that nitrous oxide anesthesia is a superior method of pain relief in patients with ischemic heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA damage induced by 3,3'-dimethoxybenzidine in liver and urinary bladder cells of rats and humans.

3,3'-Dimethoxybenzidine (DMB), a congener of benzidine used in the dye industry and previously found to be carcinogenic in rats, was evaluated for its genotoxic activity in primary cultures of rat and human hepatocytes and of cells from human urinary bladder mucosa, as well as in liver and bladder mucosa of intact rats. A similar modest dose-dependent frequency of DNA fragmentation was revealed by the alkaline elution technique in metabolically competent primary cultures of both rat and human hepatocytes exposed for 20 h to subtoxic DMB concentrations ranging from 56 to 180 microM. Replicating rat hepatocytes displayed a modest increase in the frequency of micronucleated cells after a 48-h exposure to 100 and 180 microM concentrations. In primary cultures of human urinary bladder mucosa cells exposed for 20 h to 100 and 180 microM DMB, the Comet assay revealed a clear-cut increase of DNA fragmentation. In rats given one-half LD50 of DMB as a single oral dose, the GSH level was reduced in both the liver and urinary bladder mucosa, whereas DNA fragmentation was detected only in the bladder mucosa. Taken as a whole, these results suggest that DMB should be considered a potentially genotoxic chemical in both rats and humans; the selective effect on the rat urinary bladder might be the consequence of pharmacokinetic behavior.

The effects of chronic exercise on anesthesia induced hepatotoxicity.

UNLABELLED: A hypoxic rat model of halothane-induced hepatotoxicity, which is known to produce liver damage, was used to determine the effects of chronic exercise on halothane-induced hepatotoxicity and on reduced hepatic glutathione (GSH) levels. Metabolism of volatile anesthetics may generate metabolites that can cause mild and transient hepatotoxicity. METHODS: Six male Sprague-Dawley rats completed a 10-wk (5 d x wk(-1)) treadmill running protocol. Twelve age-matched animals were used as sedentary controls. After the completion of exercise training, rats were exposed for 2 h to 1% halothane in 14% O2. Twenty-four hours later, animals were anesthetized with sodium pentobarbital and sacrificed. Livers were excised, stained, and evaluated for hepatotoxicity using a histopathological 0 (normal) to 5 (severe damage) point categorical scale and for the determination of GSH levels. RESULTS: Median histopathologic scores revealed significantly lower indications of hepatotoxicity in exercise animals as compared with control animals (score = 0.25 vs 1.50; P < 0.05). Liver damages scores between 1 and 5 were observed in 75% (9 of 12) of the control animals, whereas only 1 of 6 exercise animals had a score greater than 1 (P < 0.05). No significant difference was observed in reduced GSH levels. CONCLUSIONS: Chronic exercise improves the detoxicant ability of the liver for halothane anesthesia as noted by the ameliorated liver damage and reduced incidence of halothane-induced hepatotoxicity in the exercise animals.

In vitro and in vivo evaluation of polyoxyethylene esters as dermal prodrugs of ketoprofen, naproxen and diclofenac.

Novel polyoxyethylene esters of ketoprofen (1(a-e)), naproxen (2(a-e)) and diclofenac (3(a-e)) were synthesized and evaluated as potential dermal prodrugs of naproxen, ketoprofen and diclofenac. These esters were obtained by coupling these drugs with polyoxyethylene glycols by a succinic acid spacer. The aqueous solubilities, lipophilicities and hydrolysis rates of esters 1(a-e), 2(a-e) and 3(a-e) were determined in a buffered solution and in porcine esterase. The permeation of these prodrugs through excised human skin was studied in vitro. Furthermore we investigated the in vivo topical anti-inflammatory activity of esters 1(d), 2(e) and 3(e), which showed the best in vitro profile, evaluating the ability of these compounds to inhibit methyl nicotinate (MN)-induced skin erythema on healthy human volunteers. Esters 1(a-e), 2(a-e) and 3(a-e) showed good water stability and rapid enzymatic cleavage and their hydrolysis rates, both chemical and enzymatic, were not significantly affected by the length of the polyoxyethylenic chain used as promoiety. Concerning in vitro percutaneous absorption studies, only esters 1(d-e), 2(d-e) and 3(c-e) showed an increased flux through stratum corneum and epidermis membranes compared to their respective parent drugs. In vivo results showed an interesting delayed and sustained activity of esters 1(d) and 3(e) compared to the parent drugs. In conclusion polyoxyethylene glycols could prove to be suitable promoieties for ketoprofen, naproxen and diclofenac design since esters 1(d-e), 2(d-e) and 3(c-e) showed some requirements (chemical stability, enzymatic lability and an increased skin permeation) needed to obtain successful dermal prodrugs. Furthermore, was observed an appreciable and sustained in vivo topical anti-inflammatory activity of esters 1(d) and 3(e), compared to the parent drugs, using MN-induced erythema in human volunteers as inflammation model.

Evaluation of in vitro percutaneous absorption of lorazepam and clonazepam from hydro-alcoholic gel formulations.

Clonazepam and lorazepam are two anxiolytics, antidepressant agents, having suitable features for transdermal delivery. The objectives of this study were to evaluate the in vitro percutaneous absorption of these drugs through excised human skin (stratum corneum and epidermis, SCE) and to determine their in vitro permeation behavior from a series of hydro-alcoholic gel formulations containing various enhancing agents. The best permeation profile was obtained for both drugs applying them together with Azone in combination with propylene glycol (PG): these enhancers were able to increase the clonazepam and lorazepam percutaneous fluxes at steady-state about threefold, compared to the free enhancer formulations (Control). To explain the mechanism of the used promoters, the benzodiazepine diffusion and partitioning coefficients from the gel containing the enhancers were calculated. The results indicated that the Azone in combination with PG could act by increasing the benzodiazepine diffusion coefficients, Transcutol increased only the SC/vehicle partition coefficients, limonene in combination with PG appeared to increase both partition and diffusion coefficients moderately, while PG did not increase both the parameters. Furthermore, to evaluate the potential application of tested benzodiazepine formulations containing Azone in combination with PG using the flux values from the in vitro experiments, the corresponding steady-state plasma concentrations (C(SS)) were calculated. The obtained calculated C(SS) values are within the lorazepam therapeutic range and suggest that transdermal delivery of this drug could be regarded as feasible.

In-vitro antioxidant and in-vivo photoprotective effect of three lyophilized extracts of Sedum telephium L. leaves.

Sedum telephium L. is a medicinal plant used in antiquity to cure many types of inflammatory skin diseases. The leaves (without the external cuticle), are used to promote healing and reduce skin inflammation and pain, and contain various components. We found two major components: flavonol glycosides and polysaccharides, with molecular weight between 13,000 and 13,500 Da. We evaluated the in-vitro antioxidant and in-vivo skin photoprotective effects of three lyophilized extracts obtained from the juice of S. telephium L. leaves: a total lyophilized juice, a lyophilized flavonolic fraction, and a lyophilized polysaccharidic fraction. Two in-vitro models were used: the bleaching of the stable 2,2-diphenyl-1-picrylhydrazyl (DPPH*) radical, and the protective effect against UV-induced peroxidation on phosphatidylcholine multilamellar vesicles, as model membranes. The antioxidant/radical scavenging activity of each lyophilized extract was also assessed in-vivo by determining their ability to reduce UVB-induced skin erythema (monitored by reflectance spectrophotometry) in healthy human volunteers. The findings of the in-vitro experiments clearly demonstrated that, unlike the lyophilized polysaccharidic fraction, the lyophilized flavonolic fraction and total lyophilized juice possess strong antioxidant/free radical scavenging properties, which are likely due to phenolic compounds. Consistent with these findings, gel formulations of both the total lyophilized juice and, to a greater degree, the lyophilized flavonolic fraction appeared to possess a strong protective effect against UV-induced skin erythema in-vivo, whereas the lyophilized polysaccharidic fraction was completely ineffective. The in-vitro and in-vivo results suggest that, both the total lyophilized juice and, in particular, the lyophilized flavonolic fraction, but not the lyophilized polysaccharidic fraction of S. telephium L. leaves, have photoprotective effects against UVB-induced skin damage.

Vehicle effects on in vitro skin permeation of thiocolchicoside.

Thiocolchicoside, a semi-synthetic derivative of colchicoside, is used in topical formulations for its anti-inflammatory and muscle-relaxant properties. The objective of this study was to evaluate the effect of a (propylene glycol diperlagonate) DPPG and (propylene glycol) PG mixture present in an innovative foam formulation (Miotens) on the flux of thiocolchicoside through excised human skin. Furthermore, the in vitro permeation behaviour of this new formulation (Miotens foam) was compared to another commercial product (Muscoril ointment) and to a control gel formulation (thiogel), both enhancer free. The best permeation profile was obtained from the foam formulation (Miotens) which was able to increase the thiocolchicoside flux about three fold compared to control formulation (thiogel) and about two fold compared to the commercial formulation Muscoril ointment.

Oligoethylene ester derivatives of ketoprofen, naproxen and diclofenac as oral prodrugs: a pharmacological evaluation.

Polyoxyethylene esters of ketoprofen (1a-e), naproxen (2a-e) and diclofenac (3a-e) were tested in vitro to determine their stability in pH 7.4 phosphate buffer and in simulated gastric fluid (pH 2.0 buffer) and their susceptibility in undergoing enzymatic cleavage in human plasma. Furthermore their in vivo antiinflammatory and analgesic activity and GI toxicity were evaluated in rodents. All the prodrugs showed a good stability both in pH 7.4 phosphate buffer and in pH 2.0 buffer. They were readily hydrolyzed by human plasma and, for each group of prodrugs, no significant difference in hydrolysis rate was observed as the length of the oligoethylene chain increased. Esters 1a-e, 2a-e and 3a-e showed an anti-inflammatory activity (expressed as inhibition percent of carrageenan-induced edema in the rat) similar to that of their respective parent drug although at higher doses. The results obtained in the writhing test in mice demonstrated that all the prodrugs tested exhibited, following acute administration, a good analgesic effect. Furthermore these esters were significantly less irritating to the gastric mucosa, although administered at doses higher than the respective parent drug.

In vitro antioxidant and in vivo photoprotective effects of a lyophilized extract of Capparis spinosa L buds.

The aim of the present study was to evaluate the in vitro antioxidant and in vivo photoprotective activities of a lyophilized extract of Capparis spinosa L. (LECS) obtained by methanolic extraction from the flowering buds of this plant. For the in vitro experiments, LECS was tested employing three different models: (a). bleaching of the stable 1,1-diphenyl-2-picrylhydrazyl radical (DPPH test); (b). peroxidation, induced by the water-soluble radical initiator 2,2'-azobis(2-amidinopropane) hydrochloride, of mixed dipalmitoylphosphatidylcholine/linoleic acid unilamellar vesicles (LUVs) (LP-LUV test); and (c). UV-induced peroxidation of phosphatidylcholine multilamellar vesicles (UV-IP test). The in vivo antioxidant/radical scavenger activity was assessed by determining the ability of topically applied LECS to reduce UVB-induced skin erythema in healthy human volunteers. From the results obtained in in vitro and in vivo tests, LECS showed a significant antioxidant effect. Furthermore, by chromatographic fractionation and spectroscopic methods, we identified the major constituents of LECS, and particularly some flavonols (kaempferol and quercetin derivatives) and hydroxycinnamic acids (caffeic acid, ferulic acid, p-cumaric acid, and cinnamic acid).

Caco-2 cell line as a model to evaluate mucoprotective proprieties.

Physical protection of mucosa surface and reduction of inflammatory processes are currently considered the main strategies in the treatment and prevention of mucosal diseases. However, the majority of models used to verify the activity of new mucoprotective agents are based on limiting instrumental assessment or the sacrifice of experimental animals. In this study, for the first time, some in vitro experimental methods using Caco-2 cell line are proposed as predicting in vivo behaviour and action of mucoprotective agents. To this purpose, hyaluronic acid and natural polysaccharides for their bioadhesive activity, hydrocortisone and natural polyphenols as anti-inflammatory agents have been chosen. The obtained results demonstrated that the techniques (Con A/o-pd assay and Franz cell system) of mucoadhesive evaluation on Caco-2 cells are useful to compare the activity of each experimental sample and to assess the adhesion time to the mucosal cell surface. Moreover, the reduction of intercellular adhesion molecule-1 (ICAM-1) expression in Caco-2 cells can be considered directly correlated to the mucosal anti-inflammatory effect induced by the hydrocortisone and natural polyphenols. In conclusion, the study supported the use of Caco-2 cell as a model to compare and investigate the effect of different active substances on the mucosa and its diseases.