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Leukocyte-and platelet-rich fibrin (L-PRF) technology allows for the preparation of strong fibrin membranes enriched with cells (activated platelets, leukocytes, circulating cells) and platelet growth factors [1]. In dentistry, the use of this autologous platelet concentrates such as L-PRF, also in association with Metronidazole (MTR), seems an innovative approach for vestibular bone grafting on the alveolar ridges [2]. In addition, Curcumin (CUR), a natural polyphenol derived from the rhizome of the Curcuma longa, could be effectiveness on tissue regeneration due to its well-known antioxidant and anti-inflammatory properties [3]. The aim of the present work was the development of bioerodible sponges loaded with CUR-solid lipid nanoparticles (NLC) and MTR, assessing in vitro and ex vivo performance together with L-PRF, for future in vivo applications for tissues regeneration in oral surgeries. Curcumin (CUR) loaded solid lipid nanoparticles (NLC) were prepared using Glycyrrhetic acid, hexadecanol, isopropyl palmitate and Tween 80 as surfactant. As method, the homogenization followed by high-frequency sonication was used. After dialysis, NLC dispersion was evaluated in term of drug loading (DL, 2.2 % w/w) and drug recovery (DR, 88% w/w). NLC, characterized by Dynamic Light Scattering, exhibited an average particle size of 121.6 nm and PDI value of 0.235, considered optimal for a colloidal nanoparticle dispersion. The PZ value of -37 mV also indicated a good stability of the system. Subsequently, a hydrophilic sponge was obtained by lyophilization of a gel based on Trehalose, Natrosol, PVP, CUR-NLC dispersion and MTR (10% w/w of solid components). The ability of sponge to release CUR and MTR when applied on L-PRF clot, obtained according to the FDA and CE approved protocol (Intra-spin®, Intra-lock, Salerno, Italy) and the aptitude of actives to penetrate and/or permeate the membrane were evaluated. L-PRF clot was mounted as membrane in Franz type diffusion cells and to the apical side the sponges were applied. At the end of experiments, the residual drugs entrapped into the L-PRF membrane were quantified by extraction. The results showed that after 3 h CUR is not able to cross the L-PRF clot, whereas a significant percentage of dose (11.4%) remains trapped inside it. MTR cross L-PRF membrane and reaches the acceptor compartment gradually. After 3 h, the 16.8% of dose reaches plasma whereas 6.5% was entrapped in membrane. In conclusion, both the CUR-NLC and the hydrophilic sponge containing MTR and CUR-NLC have been successfully prepared. When applied on L-PRF membrane, the sponges release the actives promoting CUR penetration and MTR permeation. The obtained results encourage further studies about the possibility to use these sponges to delivery antioxidant and antimicrobial agents to support bone regeneration on surgical sites of teeth extraction treated with L-PRF.

Rewarding and reinforcing properties of alcohol are mediated by activation of the mesolimbic dopaminergic system1. This neurosystem is hypofunctional in the addicted brain, even beyond somatic and psychological signs of withdrawal. Boosting strategy on the dopaminergic tone could represent a valid approach to alcohol addiction treatment2. The effects of a new dopamine conjugate3 (2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide, DA-Phen) on operant behaviour and on withdrawal behaviour, following alcohol deprivation, were evaluated. The concentration of acetaldehyde (ACD), ethanol's first metabolite, as an indirect measure of the possible DA-Phen modulation in alcohol consumption, was also assessed. Male Wistar rats were tested in an operant paradigm, made by different phases: Habituation (Ethanol 5%), Training (Ethanol 20%), Extinction and Deprivation/Relapse (3 cycles). Rats were treated with DA-Phen (0.03 mmol/kg i.p) during abstinence, or during relapse. Behavioural reactivity and anxiety-like behaviour during withdrawal were also evaluated. At the end of described paradigm, animals were sacrificed, and DA-Phen distribution in organ homogenates was detected and quantified. Da-Phen promoted a reduction in alcohol intake by 50% from the second day of relapse (p

Rewarding and reinforcing properties of alcohol have been shown to be mediated by activation of the mesolimbic dopaminergic system. Experimental evidences suggest that mesolimbic dopamine system is hypofunctional in addicted brain; further, reduced dopaminergic activity outlasts somatic signs of withdrawal and may drive craving and relapse. Boosting strategy on dopaminergic neurons could represent a valid therapy. Effects of pharmacological manipulation of brain Dopaminergic receptors by a new dopamine conjugate, Phenylalanine-β(3,4dihydroxyphenyl)-etilamide (DA-Phen), on operant behaviour and on both acute and prolonged withdrawal symptoms during ethanol abstinence have been evaluated. Male Wistar rats were tested in an operant conditioning task: they were subjected to Habituation (Ethanol 5%), Training (Ethanol 20%), and Extinction sessions. Then, three cycles of Deprivation/Relapse were performed. Rats were administered with DA-Phen (0.03mmol/kg i.p) during abstinence, or during relapse, 2h prior the operant task session. Locomotor activity and anxiety-like behaviour during withdrawal were also evaluated. Da-Phen, administered during abstinence phase, or during relapse, was able to reduce alcoholic intake pattern by 50% from the second day of operant conditioning task (p

Since the activity of several conventional anticancer drugs is restricted by resistance mechanisms and dose-limiting side-effects, the design of formulations for local application on malignant lesions seems to be an efficient and promising drug delivery approach. In this study, the effect of locally applied 5-FU on cell death was evaluated both in a SCC4/HEK001 model and in a newly proposed 3D outgrowth model of oral squamous cell carcinoma (OSCC). Initially, the optimal drug dose was established by delivery of solutions containing different amounts of 5-FU. The solution containing 1% (w/v) of 5-FU resulted effective in inducing cell death with complete eradication of cell colonies. Buccal tablets were designed to deliver 5-FU locoregionally to the cancer lesions of the oral cavity. Tablets were prepared using a drug loaded matrix of acrylic/methacrylic acid copolymer containing 1% (w/w) of 5-FU and applied on 3D outgrowths. The drug release from tablets appeared to be sufficient to induce cell death as confirmed by transmission electron microscopy and enzymatic assay (TUNEL). After 120 h of treatment, when about 90% of the drug had been discharged from the tablets into the culture environment, 5-FU caused loss of cell-cell communications and apoptotic cell death. After 192 h, a complete disaggregation of the 3D oral outgrowths and the death of all the cells was observed. Buccal matrix tablets could be considered a promising new approach to the locoregional treatment of OSCC. Risks of systemic toxicity are avoided since very low drug doses are delivered.

In recent years, with the increased use of antibiotics and immunosuppres-sive agents, there was an increased incidence of oral mycosis and Candida albicans is the most common etiologic agent in oropharyngeal candidiasis, especially in patients with HIV. The aim of this work is to develop a new dosage form containing miconazole (MN) to be topically applied on oral mucosa, allowing for a massive penetration of the drug in the tissue. The vehicle for the drug delivery was lipid microparticles incorporated in a hydrophilic gel. The lipospheres were obtained by hot melt encapsulation method using as matrix ingredients a mixtures of esters of fatty acids with higher fatty alcohols, having low melting point and a composition similar to that of some lipid membrane components The microparticles were characterized for particle size (by laser light scattering), entrapment efficiency (by UV-Vis analysis) morphology (optical microscopy) and physical state (DSC) The hydrophilic gel contained also lemon essence to enhance the palatability of product and increase the compliance of patient. The oral tissue penetration of MN released from the lipospheres alone or incorporated in gel was evaluated ex-vivo using franz diffusion cell and buccal porcine mucosa. The results were compared with behaviour of commercial Daktarin® oral gel. The lipid microparticles increase significantly the accumulative uptake of MN in buccal mucosa over the marketed gel and showed a considerably enhanced mucosa targeting effect, even at very low doses. These results indicate that the studied lipospheres/gel formulation may be a promising carrier for topical delivery of MN in the oral cavity.

At present, neuroscience literature dealing with Acetaldehyde (ACD), ethanol first metabolite, as a drug of abuse, reported conditioned taste aversion paradigm and conditioned place preference, following ICV or i.p. administration. No reports exist on ACD oral self-administration probably because of its high volatility. For this reason, this pilot study was aimed at the evaluation of ACD concentration in aqueous solutions, and consequently to the rat drinking behaviour when acetaldehyde was presented in a free-access paradigm together with water and a sweet solution. Preliminarly we investigated the loss of ACD content in aqueous standard solutions. For the investigation of ACD concentration, all standard samples (ACD concentration ranging from 2 to 90 mM) were analysed in triplicate at regular time intervals (t = 0 h,12 h, 24 h and 48h.) using UV-Vis method at ? = 276 nm. Despite of ACD great volatility, no appreciable loss of ACD has been found in all solutions tested. When adult male Wistar rats were subjected to a three bottle choice paradigm with ACD 9mM, saccharin 0,125% (w/v) plus methyl-paraben 0,1% (w/v), and tap water, the amount of fluid intake was monitored every 24 h, and bottles were refilled every day with fresh solutions. Our results demonstrate that rats do self-administer ACD, even in the presence of a sweet solution and that their preference toward the ACD gradually increases day by day. In conclusion our pilot study shows for the first time that ACD concentration is maintained in an aqueous solution within 24 hours and that rats spontaneously self-administer ACD in a free-access paradigm even in the presence of a saccharin solution, providing further evidence of the addictive properties of ACD.