Francesca Baratta

Development of O/W nanoemulsions for ophthalmic administration of timolol.

After an initial screening of ingredients and production methods, nanoemulsions for ocular administration of timolol containing the drug as maleate (TM) or as ion-pair with AOT (TM/AOT) were prepared. The physico-chemical characterization of nanoemulsions, regarding mean diameter, pH, zeta potential, osmolarity, viscosity and surface tension, underlined their feasibility to be instilled into the eyes. Single components and emulsions were tested ex vivo on rabbit corneas to evaluate corneal irritation, that was measured according to opacity test. A marked decrease in corneal opacity was observed using the drug formulated in nanoemulsions rather than in aqueous solutions. Drug permeation and accumulation studies were performed on excised rabbit corneas. An increase in drug permeation through and accumulation into the corneas were observed using TM-AOT compared to TM due to an increase of lipophilicity of the drug as ion-pair. The introduction of chitosan (a positive charged mucoadhesive polymer) into emulsions allowed to increase TM permeation probably due to the interaction of chitosan with corneal epithelial cells.

A randomized double-blind placebo controlled phase I-II study on clinical and molecular effects of dietary supplements in men with precancerous prostatic lesions. Chemoprevention or "chemopromotion"?

Antioxidants effectiveness in prostate cancer (PCa) chemoprevention has been severely questioned, especially after the recent results of the Selenium and Vitamin E Cancer Prevention Trial. We present the results of a double‐blind randomized controlled trial (dbRCT) on the pharmacokinetic, clinical, and molecular activity of dietary supplements containing lycopene, selenium, and green tea catechins (GTCs) in men with multifocal high grade prostatic intraepithelial neoplasia (mHGPIN) and/or atypical small acinar proliferation (ASAP).

Diffusion of counterfeit drugs in developing countries and stability of galenics stored for months under different conditions of temperature and relative humidity

Aim To investigate the diffusion of counterfeit medicines in developing countries and to verify the stability of galenic dosage forms to determine the stability of galenics prepared and stored in developing countries. Methods We purchased 221 pharmaceutical samples belonging to different therapeutic classes both in authorized and illegal pharmacies and subjected them to European Pharmacopoeia, 7th ed. quality tests. An UV-visible spectrophotometric assay was used to determine the galenics stability under different conditions of temperature (T) and relative humidity (RH). Results A substantial percentage of samples was substandard (52%) and thus had to be considered as counterfeit. Stability tests for galenics showed that the tested dosage forms were stable for 24 months under “standard” (t = 25 ± 2°C, RH = 50 ± 5%) conditions. Under “accelerated” (t = 40 ± 2°C, RH = 50 ± 5%) conditions, samples were stable for 3 months provided that they were stored in glass containers. Stability results of samples stored in “accelerated” conditions were similar to those obtained by on site in tropical countries and could so supply precious information on the expected stability of galenics in tropical countries. Conclusion This study gives useful information about the presence of counterfeit medicinal products in the pharmacies of many developing countries. This should serve as an alarm bell and an input for the production of galenics. We recommend setting up of galenic laboratories in developing countries around the globe.

Protective Effects of Pyridoxamine Supplementation in the Early Stages of Diet-Induced Kidney Dysfunction

Pyridoxamine, a structural analog of vitamin B6 that exerts antiglycative effects, has been proposed as supplementary approach in patients with initial diabetic nephropathy. However, the molecular mechanism(s) underlying its protective role has been so far slightly examined. C57Bl/6J mice were fed with a standard diet (SD) or a diet enriched in fat and fructose (HD) for 12 weeks. After 3 weeks, two subgroups of SD and HD mice started pyridoxamine supplementation (150 mg/kg/day) in the drinking water. HD fed mice showed increased body weight and impaired glucose tolerance, whereas pyridoxamine administration significantly improved insulin sensitivity, but not body weight, and reduced diet-induced increase in serum creatinine and urine albumin. Kidney morphology of HD fed mice showed strong vacuolar degeneration and loss of tubule brush border, associated with a drastic increase in both advanced glycation end products (AGEs) and AGEs receptor (RAGE). These effects were significantly counteracted by pyridoxamine, with consequent reduction of the diet-induced overactivation of NF-kB and Rho/ROCK pathways. Overall, the present study demonstrates for the first time that the administration of the antiglycative compound pyridoxamine can reduce the early stages of diet-dependent kidney injury and dysfunction by interfering at many levels with the profibrotic signaling and inflammatory cascades.

Reduced Susceptibility to Sugar-Induced Metabolic Derangements and Impairments of Myocardial Redox Signaling in Mice Chronically Fed with D-Tagatose when Compared to Fructose

Background D-tagatose is an isomer of fructose and is ~90% as sweet as sucrose with less caloric value. Nowadays, D-tagatose is used as a nutritive or low-calorie sweetener. Despite clinical findings suggesting that D-tagatose could be beneficial in subjects with type 2 diabetes, there are no experimental data comparing D-tagatose with fructose, in terms of metabolic derangements and related molecular mechanisms evoked by chronic exposure to these two monosaccharides. Materials and methods C57Bl/6j mice were fed with a control diet plus water (CD), a control diet plus 30% fructose syrup (L-Fr), a 30% fructose solid diet plus water (S-Fr), a control diet plus 30% D-tagatose syrup (L-Tg), or a 30% D-tagatose solid diet plus water (S-Tg), during 24 weeks. Results Both solid and liquid fructose feeding led to increased body weight, abnormal systemic glucose homeostasis, and an altered lipid profile. These effects were associated with vigorous increase in oxidative markers. None of these metabolic abnormalities were detected when mice were fed with both the solid and liquid D-tagatose diets, either at the systemic or at the local level. Interestingly, both fructose formulations led to significant Advanced Glycation End Products (AGEs) accumulation in mouse hearts, as well as a robust increase in both myocardial AGE receptor (RAGE) expression and NF-κB activation. In contrast, no toxicological effects were shown in hearts of mice chronically exposed to liquid or solid D-tagatose. Conclusion Our results clearly suggest that chronic overconsumption of D-tagatose in both formulations, liquid or solid, does not exert the same deleterious metabolic derangements evoked by fructose administration, due to differences in carbohydrate interference with selective proinflammatory and oxidative stress cascades.