Pulsed release of antidepressants from nanocomposite hydrogels

The pulsed release of three antidepressants (paroxetine, duloxetine, vortioxetine), loaded on two vinyl hydrogels bearing -amino acid residues (L-phenylalanine, L-valine) and embedded magnetic nanoparticles, was evaluated in different buffer solutions of purposely chosen pHs (2.9, 4.6, and 7.4). At low pH values the release of the drug was always small for a long period of days, and it underwent a sudden increase when a solution of pH 7.4 was maintained for a short period of hours. The releasing increase becomes much higher as greater was the residence time of the solution in contact with the hydrogel. The application of an alternating magnetic field (AMF) further increases the amount of drug released during the pH pulses. These different release variations were related to a different and reversible ability to swell of the hydrogel. The mechanism behind the process was mainly due to the different acid/base behaviour of the free carboxyl groups

Smart polyelectrolyte hydrogels: a novel platform for drug delivery

Three kinds of vinyl hydrogels with a-aminoacid residues have been considered as potential platforms for the deliver of several therapies (pain, diabetes, and mood) when loaded with appropriate drugs. The presence of ionizable groups of the L-valine, L-phenylalanine and L-histidine residues is able to modify the swelling properties of the hydrogel on the basis of its pKa values. A greater basicity constant of the functional groups improves a greater loading of the drug and a longer sustained-release pattern due to a strong polymer-drug ionic interaction. This occurs for the insulin and the paroxetine loaded on carboxylate hydrogels, and diclofenac loaded on zwitterionic hydrogels. The pH stimulation improves the swelling of the hydrogel and increases ‘on demand' the drug availability. A further remote stimulus based on alternating magnetic fields (AMF) on hydrogels containing embedded magnetic nanoparticles (CoFe2O4) allows a greater release rate of insulin and paroxetine for several pulses at physiological pH

Critical issues and opportunities of emergency psychiatry in Italian emergency departments

In Italy emergency physicians are the front line of care for patients with medical conditions such as trauma, heart attacks, strokes or psychiatric disorders. Triage represents the first clinical contact with the person to determine urgency of care, and includes initial risk assessment and determination of observation level. It is necessary to undertake mental health triage for all service users on entry to the Emergency Department (ED), alongside physical health triage. The recourse to emergency services for psychiatric complaints is increasing and ED providers are often the first contact a patient will have with psychiatric care. The organization of Italian EDs is constantly evolving under the pressure of various external forces (population aging, increasing use of new substances, immigration, choices of economic policy, and technological development). The psychiatric emergency service contact represents a key to addressing the presenting problem and it is a critical link for continuity of care. The management of psychiatric disorders is an evolving issue in Italy as in other countries. Research increasingly suggests the importance of specific training for EDs teams in order to provide appropriate handling in acute settings. Psychiatrists and ED physicians can – and should – play a fundamental role in promoting a targeted and shared training for emergency services to deal with crisis according to evidence-based medicine. Service organization, legal issues, safety, training and education are not well defined and established and still imply improvisation, while they deserve attention as fundamental prerequisite to implement specific treatment guidelines

Antibacterial Properties of Silver Nanoparticles Embedded on Polyelectrolyte Hydrogels Based on α-Amino Acid Residues

Polyelectrolyte hydrogels bearing L-phenylalanine (PHE), L-valine (AVA), and L-histidine (Hist) residues were used as scaffolds for the formation of silver nanoparticles by reduction of Ag+ ions with NaBH4. The interaction with the metal ion allowed a prompt collapse of the swollen hydrogel, due to the neutralization reaction of basic groups present on the polymer. The imidazole nitrogen of the hydrogel with Hist demonstrated greater complexing capacity with the Ag+ ion comparedtothehydrogelswithcarboxylgroups. Thesubsequentreductiontometallicsilverallowed for the restoration of the hydrogel’s degree of swelling to the starting value. Transmission electron microscopy (TEM) and spectroscopic analyses showed, respectively, a uniform distribution of the 15 nm spherical silver nanoparticles embedded on the hydrogel and peak optical properties around a wavelength of 400 nm due to the surface plasmonic effect. Unlike native hydrogels, the composite hydrogels containing silver nanoparticles showed good antibacterial activity as gram+/gram− bactericides, and higher antifungal activity against S. cerevisiae

Light therapy as a treatment for sexual dysfunctions -beyond a pilot study

Summary Aim. Seasonal trends were demonstrated in reproduction and sexual activity. Through the secretion of melatonin the pineal gland plays an important role, in the neuroendocrine control of sexual function and reproductive physiology. We hypothesized that inhibition of the pineal gland activity through a light treatment may favorably affect sexual function. Method. We recruited 24 subjects with a diagnosis of hypoactive sexual desire disorder and / or primary sexual arousal disorder. The subjects were randomly assigned to either active light treatment (ALT) or placebo light treatment (L-PBO). Participants were assessed during the first evaluation and after 2 weeks of treatment, using the Structured Clinical Interview for Sexual Disorders DSM-IV (SCID-S) and a self-administered rating scale of the level of sexual satisfaction (1 to 10). Repeated measures ANOVA were performed to compare the two groups of patients. Post-hoc analysis was performed by Holm-Sidak test for repeated comparisons. Results. At baseline the two groups were comparable. After 2 weeks the group treated with Light Therapy showed a significant improvement in sexual satisfaction, about 3 times higher than the group that received placebo, while no significant improvement was observed in the group L-PBO. Conclusions. Our results confirm a potentially beneficial effect of Light Therapy on primary sexual dysfunction. In the future, we propose to correlate clinical findings with testosterone levels pre / post treatment

Nationwide consensus on the clinical management of treatment-resistant depression in Italy: a Delphi panel

Background: Treatment-resistant depression (TRD) is defined by the European Medicines Agency as a lack of clinically meaningful improvement after treatment, with at least two different antidepressants. Individual, familiar, and socio-economic burden of TRD is huge. Given the lack of clear guidelines, the large variability of TRD approaches across different countries and the availability of new medications to meet the need of effective and rapid acting therapeutic strategies, it is important to understand the consensus regarding the clinical characteristics and treatment pathways of patients with TRD in Italian routine clinical practice, particularly in view of the recent availability of esketamine nasal spray. Methods: A Delphi questionnaire with 17 statements (with a 7 points Likert scale for agreement) was administered via a customized web-based platform to Italian psychiatrists with at least 5 years of experience and specific expertise in the field of depression. In the second-round physicians were asked to answer the same statements considering the interquartile range of each question as an index of their colleagues' responses. Stata 16.1 software was used for the analyses. Results: Sixty panellists, representative of the Italian territory, answered the questionnaire at the first round. For 8/17 statements more than 75% of panellists reached agreement and a high consensus as they assigned similar scores; for 4 statements the panellists assigned similar scores but in the middle of the Likert scale showing a moderate agreement with the statement, while for 5 statements there was indecision in the agreement and low consensus with the statement. Conclusions: This Delphi Panel showed that there is a wide heterogeneity in Italy in the management of TRD patients, and a compelling need of standardised strategies and treatments specifically approved for TRD. A high level of consensus and agreement was obtained about the importance of adding lithium and/or antipsychotics as augmentation therapies and in the meantime about the need for long-term maintenance therapy. A high level of consensus and agreement was equally reached for the identification of esketamine nasal spray as the best option for TRD patients and for the possibility to administrate without difficulties esketamine in a community outpatient setting, highlighting the benefit of an appropriate educational support for patients

Controlled Release of Antidepressant Drugs by Multiple Stimuli-Sensitive Hydrogels Based on α-Aminoacid Residues

2noTwo slightly cross-linked hydrogels bearing l-phenylalanine (Phe-Nip3) or l-valine (Ava2) residues of a copolymeric and homopolymeric vinyl structure were considered for their potential application in the psychiatric treatment of depression. Two antidepressant drugs (citalopram and trazodone) were loaded into hydrogels and their controlled release behavior monitored for several days at 25 °C in two buffer solutions of different pHs (PBS pH 7.4 and acetate pH 4.6). The different basicity constants (logKs) of the involved substance determine a different electrostatic effect between the drug ionized positively and the negatively charged hydrogel. Both the hydrogels loaded with citalopram showed a greater binding effect with respect to trazodone. In fact, for the same hydrogel, the release of citalopram in PBS (4 days) was slower than trazodone (24 h). In addition, at pH (4.6) < logK the release of the drug was much slower and durable, due to the lower capacity of ionization and swelling of the hydrogel. Additionally, the magnetic nanoparticles (CoFe2O4) embedded into the hydrogel Phe-Nip3 were an additional remote control for drug release through the stimulation of an appropriate alternating magnetic field (AMF, 20 kHz and 50 W). In these conditions, the kinetics of the drug released was substantially increased.nonemixedCasolaro, Mario; Casolaro, IlariaCasolaro, Mario; Casolaro, Ilari