Biodegradable microspheres loaded with an anti-Parkinson prodrug: an in vivo pharmacokinetic study.

During chronic treatment with L-dopa (LD), Parkinsonian patients often experience uncontrolled motor complications due to fluctuations of the plasmatic levels of LD that result in pulsatile dopaminergic stimulation. To overcome these plasmatic fluctuations, a novel prodrug of LD, L-dopa-α-lipoic acid (LD-LA), has been proposed as a tool for achieving continuous dopaminergic stimulation. Due to slower susceptibility toward enzymatic conversion by LD-degrading enzymes (such as catechol-O-methyltransferase and monoamine oxidase), the plasma half-life of this prodrug is longer than that of LD. Moreover, the higher lipophilicity of LD-LA over LD promotes its delivery to the CNS, where the resulting levels of dopamine (DA) are kept high for a longer time than after equimolar administration of LD. To further reduce fluctuations in plasma levels of LD, LD-LA has been entrapped into biodegradable polymeric microspheres to be used as a depot system with the aim to prevent prodrug degradation and to obtain a sustained release of the intact compound. In the present work, a formulation of LD-LA loaded microspheres (characterized for drug loading, size, morphology, thermal properties, and in vitro prodrug release) has been administered subcutaneously to rats, and the resulting levels of LD and DA in plasma and striatal tissue, respectively, have been monitored. A good correlation between the in vitro release kinetics and the time range during which the formulation alters the LD/DA tissue levels in vivo was observed, suggesting that the polymeric microsphere matrix protects the loaded prodrug from chemical and enzymatic degradation and controls its release. Interestingly, LD-LA microspheres provided sustained levels of DA neurotransmitter in the striatum nucleus for up to 4 days after a single administration. In conclusion, a polymeric microsphere formulation of LD-LA is an attractive medicine for treating Parkinson's disease (PD) symptoms, avoiding motor complications.

The use of customized mouthguards during the training produced protective effects on salivary factors of young athletes.

AIM: Custom-made mouthguards have many advantages compared to the stock and ready-made types, but sport treatments with custom made mouthguards involve changes in ecological factors of the oral cavity. In the present study we investigated the potential protective role of salivary factors, such as pH value, volume, prostaglandin E2 (PGE2) and 8-iso-prostaglandin F2? (8-iso-PGF2?) levels during training with customised mouthguards. MATERIALS AND METHODS: A total of 80 subjects were selected: 40 athletes, of whom 20 practice volleyball and 20 basketball (test group), and 40 subjects who attend a gym at a non-competitive level (control group). The athletes (test group) were analyzed at baseline (T0), pre-training (T1), post-training with custom-made Ethylene-Vinyl-Acetate (EVA) mouthguards (T2), post-training without mouthguards (T3). The control group was analyzed only at baseline (T0). On each player, in the 4 time points, and on the control group at T0, we stimulated saliva for determining PGE2 and 8-iso-PGF2? levels by radioimmunoassay and pH value by a pH meter and volume/ml. Saliva pH was calculated with a pH meter. RESULTS: We observed an inhibition of 8-iso-PGF2? salivary release induced by physical exercise and by use of custom-made mouthguard, while we found an increase in PGE2 salivary level in athletes after training and wearing the mouthguard. Furthermore, in the test of the volume of saliva produced in 5 minutes, a significant inhibition of saliva production emerged in the athletes who did not use the mouthguard during sports activities. CONCLUSION: Sports activity could lead to a reduction in oxidative stress and the use of mouth guards seems even more effective for athletes.