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Oral squamous cell carcinoma (OSCC) develops slowly and it is usually preceded by identifiable oral preneoplastic lesions (OPLs): chemoprevention could be a promising approach. Resveratrol (RV) is a plant-based agent characterized by a strong in vitro antineoplastic action, but this effect has not been clinically confirmed owing to its metabolic inactivation. In order to circumvent this limitation and to improve RV efficacy, it was locally applied and complexed with a protective and solubilising vehicle (2-hydroxypropyl-beta-cyclodextrin, HPbetaCD). The experimentation was performed in vitro on 7,12-dimethylbenz[a]anthracene-induced hamster OSCC cell line (HCPC I) and in vivo in the related animal model, by comparison of two RV-HPbetaCD formulations (cream and mouthwash) and RV alone. Vehicles and RV-formulations were free from toxicity. Antiproliferative action of RV on HCPC I was concentration- and time-dependent, and was improved in HPbetaCD-formulations. In vivo, RV prevented OPL and OSCC appearance and growth. Here, too, HPbetaCD-formulations (mainly mouthwash) demonstrated the best chemopreventive effects in terms of lesions prevalence, multiplicity, dimension, and histological signs of malignancy. HPLC detection of RV corroborated that its action is concentration-correlated and is improved by its inclusion in HPbetaCDs. In summary, our study demonstrates that RV is effective in the chemoprevention of DMBA-induced oral carcinogenesis and when it is complexed with HPbetaCDs its efficacy is significantly improved.

The effect of some additives, phenylalanine, ascorbyl palmitate and sodium ascorbyl phosphate on the oxidation of linoleic acid and porcine ear skin induced by UV irradiation was investigated, in the absence and in the presence of variously uncoated and coated titania powders. Such additives have, on the one hand, a scavenging activity toward the oxidizing species photogenerated by TiO(2), and on the other one an inhibitory effect toward UVB-induced peroxidation. Sodium ascorbyl phosphate and ascorbyl palmitate displayed a stronger antioxidant effect than phenylalanine toward linoleic acid peroxidation. On porcine skin all the three molecules exhibited both antiradical and antioxidant activity. Their protective effect against peroxidation was higher with porcine skin lipids than with linoleic acid, referable to the chemical differences in the two lipid substrates.

TiO(2) nanoparticles hazard is associated to their photocatalytic activity causing release of DNA damaging ROS (Reactive Oxygen Species), lipid peroxidation and skin damage. Various coatings have been proposed to minimize photocatalysis, while keeping the potential to block UV radiations. Uncoated and variously coated commercial nano-titania have been classified on the basis of UVB-induced lipoperoxidation of linoleic acid. A selection of the most and the least protective specimens was then examined by ESR (Electron Spin Resonance) to evidence the presence of surface paramagnetic centres and the release of ROS in aqueous suspensions (spin trapping). Paramagnetic centres and ROS were correlated with the extent of lipid peroxidation. When tested on porcine skin (mimicking the human one), titania acted as on linoleic acid. The combined use of lipid peroxidation of simple fatty acids with ESR analysis is here proposed as a possible screening tool for the evaluation of the potential toxicity of nano-titania in sunscreen preparations.

The effect of selected organic and inorganic compounds, present in snow and cloudwater was studied. Photolysis of solutions of nitrate to nitrite was carried out in the laboratory using a UVB light source. The photolysis and other reactions were then modelled. It is shown that formate, formaldehyde, methanesulphonate, and chloride to a lesser extent, can increase the initial formation rate of nitrite. The effect, particularly significant for formate and formaldehyde, is unlikely to be caused by scavenging of hydroxyl radicals. The experimental data obtained in this work suggest that possible causes are the reduction of nitrogen dioxide and nitrate by radical species formed on photooxidation of the organic compounds. Hydroxyl scavenging by organic and inorganic compounds would not affect the initial formation rate of nitrite, but would protect it from oxidation, therefore, increasing the concentration values reached at long irradiation times. The described processes can be relevant to cloudwater and the quasi-liquid layer on the surface of ice and snow, considering that in the polar regions irradiated snow layers are important sources of nitrous acid to the atmosphere. Formate and (at a lesser extent) formaldehyde are the compounds that play the major role in the described processes of nitrite/nitrous acid photoformation by initial rate enhancement and hydroxyl scavenging.

Deformable liposomes were prepared to investigate the effectiveness of dermal administration of methotrexate (MTX). The phospholipids used to prepare the liposomes were soybean lecithin (PC) or hydrogenated lecithin (HPC) and dipotassium glycyrrhizinate (KG) as surfactant. The lipid/KG ratio (w/w) was 2:1 and 4:1. Liposomes size, entrapment efficiency and MTX release through dialysis membrane were determined and the interaction between MTX and liposomes was investigated using differential scanning calorimetry. The MTX amount permeated through pig skin were three- to four-fold higher using liposomes containing KG compared to those from water solution or normal liposomes. No significant differences were observed between PC-KG liposomes and HPC-KG liposomes. At the end of the skin permeation assay using deformable liposomes, up to 50% of the administered dose was found in the skin. This capability depends on the self-regulating carrier deformability. These results suggest that liposomes containing KG may be of value for the topical administration of MTX in the treatment of psoriasis.

Nanoparticles of griseofulvin, a model drug with poor solubility and low bioavailability, were prepared from water dilutable microemulsions by the solvent diffusion technique. Solvent-in-water microemulsion formulations containing water, butyl lactate, lecithin, taurodeoxycholate sodium salt (TDC) or dipotassium glycyrrhizinate (KG), 1,2-propanediol or ethanol were used. The formation of macroscopically homogeneous, stable, fluid, optically transparent, isotropic solutions (microemulsions) was investigated by constructing pseudo-ternary phase diagrams. In the presence of TDC or KG, microemulsion systems that remained transparent on water dilution could be obtained. The displacement of butyl lactate, with an excess of water, from the internal phase of the microemulsions containing the drug into the external phase, lead to successful fabrication of drug nanosuspensions. Nanoparticle size was dependent on microemulsion composition: using KG, griseofulvin nanoparticles below 100 nm with low polydispersity and an increased dissolution rate were obtained., (Copyright 2003 Elsevier Science B.V.)