Effect of chitinase inhibitors on endotoxin-induced uveitis (EIU) in rabbits

The acidic mammalian chitinase (AMCase) is significantly increased in tears of human allergic conjunctivitis. The aim of the study was to investigate the effects of chitinase inhibitors, allosamidin and caffeine versus dexamethasone, in rabbit endotoxin-induced uveitis (EIU). EIU was induced in rabbits by a single intravitreal injection of 100 ng/10 μl lipopolysaccharide (LPS). Drugs at four different concentrations (0.1, 0.01, 0.001 and 0.0001 mM) were topically applied to the rabbit eye five times in 24 h. Tears were collected at 0, 6 and 24 h after LPS to measure the AMCase activity. The effect of treatment was also evaluated at the same time by slit lamp examination. Tear AMCase activity increased 6 and 24 h after LPS injection. The AMCase activity was significantly inhibited in all treated groups with all doses of allosamidin and caffeine except with the lowest concentration. A higher AMCase inhibition at 24 h was found with allosamidin and caffeine compared to dexamethasone. Moreover, topical administration of allosamidin, caffeine and dexamethasone produced a remarkable reduction of inflammatory signs, in the order: dexamethasone > caffeine > allosamidin. AMCase inhibitors showed in this rabbit model of uveitis a notable control of inflammatory response with a significant reduction of AMCase activity in tears with caffeine and allosamidin. These results support the key role of AMCase in the pathogenesis of human ocular inflammatory diseases and the therapeutic effect of AMCase inhibitors on experimental uveitis

Novel polysaccharides-based viscoelastic formulations for ophthalmic surgery: rheological characterization.

Different formulations based on bioadhesive and biocompatible polymers, hydroxypropylmethylcellulose (HPMC), sodium hyaluronate (SH) and chitosan glutamate (CG), were prepared to be potentially used as ophthalmic viscosurgical device (OVD) during cataract surgery. Their rheological properties were analyzed in terms of flow and oscillation properties and compared to a commercially available OVD, widely employed in cataract surgery, named Viscoat. All the formulations tested presented a pseudoplastic behavior during flow. Primary systems containing HPMC or CG and HPMC/CG binary systems behaved as viscous solution (G''>G') over the range of oscillatory frequencies observed, while the primary systems containing SH and HPMC/SH binary formulations and showed an entangled network behavior when subjected to a sinusoidal stress. By increasing the SH concentration in the binary systems, the viscoelastic parameters, G'and G'', and zero frequency viscosity (derived from the Cross model) increased. Viscoat presents viscoelastic parameters values lower than the corresponding values of all the binary formulations of HPMC/SH and higher than all the formulations made up of CG and HPMC. As regard to HPMC/SH binary system, the cross-over frequency decreased by increasing SH concentration in the systems and it was the highest for Viscoat and thus the opposite occurred for the relaxation time. The rheological synergy in the binary formulations was assessed by calculating the interaction parameters which increased as a function of SH and CG concentration in the binary systems. The values of the interaction parameters of the formulations based on CG, are lower than 10 Pa indicating that they did not interact synergically while the formulations based on SH show high values of the interactions parameters (in the range from 55 to 130 Pa). This indicates that secondary bonds formation occurs between SH and HPMC. From the rheological analysis it can be concluded that the binary formulations based on CG do not possess appropriate features to be used as OVD while both the viscoelastic and the flow properties of the binary formulations made up of SH and HPMC are suitable for their application as OVD being able to maintain the ocular spaces and to be easily administrated. Moreover, thank to the adhesive properties of both components, the binary formulation should be able to interact with corneal endothelium so offering a durable protection to ocular tissue. On the basis of the rheological characterization presented in this work, we concluded that the binary system named VISC26 (HPMC at 0.8\% and SH at 2.3\%) represents the formulation that better fulfill the OVD requirements

Preparation and characterization of Eudragit Retard nanosuspensions for the ocular delivery of cloricromene

The purpose of this study was to improve the stability of cloricromene (AD6) in ophthalmic formulations and its drug availability at the ocular level. To this end, AD6-loaded polymeric nanoparticle suspensions were made using inert polymer resins (Eudragit RS100 and RL100). We modified the quasi-emulsion solvent diffusion technique by varying some formulation parameters (the drug-to-polymer ratio, the total drug and polymer amount, and the stirring speed). The chemical stability of AD6 in the nanosuspensions was assessed by preparing some formulations using (unbuffered) isotonic saline or a pH 7 phosphate buffer solution as the dispersing medium. The formulations were stored at 4°C, and the rate of degradation of AD6 was followed by high performance liquid chromatography (HPLC). The obtained nanosuspensions showed mean sizes and a positive surface charge (ζ-potential) that make them suitable for an ophthalmic application; these properties were maintained upon storage at 4°C for several months. In vitro dissolution tests confirmed a modified release of the drug from the polymer matrixes. Nanosuspensions prepared with saline solution and no or lower amounts of surfactant (Tween 80) showed an enhanced stability of the ester drug for several months, with respect to an AD6 aqueous solution. Based on the tecnological results, AD6-loaded Eudragit Retard nanoparticle suspensions appear to, offer promise as a means to improving the shelf life and bioavailability of this drug after ophthalmic application

Villard:17. Inversione di sguoardi/sbarchi. Migrazioni Accoglienza Intercultura. L'architettura delle nuove centralità urbane

In continuità con il tema “Territori strategici, antichi sbarchi e nuove mete di libertà" dal seminario Villard 16, la riflessione progettuale si sposta sulle trasformazioni dei caratteri rappresentativi delle grandi città indotte da un’ormai acquisita, diffusa, multiculturalità. Le forme della sua rappresentazione trovano un inedito campo di sperimentazione architettonica in una Napoli metropolitana che ormai include a pieno titolo paesaggi urbani eterogenei costruiti storicamente da antichi fenomeni migratori e da più recenti utopie colonialistiche. All’interno di una straordinaria cornice geomorfologica, citazioni, analogie, ibridazioni con altri mondi mediterranei costituiscono il punto di partenza di nuove composizioni urbane e architettoniche espressione di una rinnovata cultura dell’abitare