Recent advances in nanosystems and strategies for vaginal delivery of antimicrobials

Vaginal infections such as bacterial vaginosis (BV), chlamydia, gonorrhea, genital herpes, candidiasis, and trichomoniasis affect millions of women each year. They are caused by an overgrowth of microorganisms, generally sexually transmitted, which in turn can be favored by alterations in the vaginal flora. Conventional treatments of these infections consist in systemic or local antimicrobial therapies. However, in the attempt to reduce adverse effects and to contrast microbial resistance and infection recurrences, many efforts have been devoted to the development of vaginal systems for the local delivery of antimicrobials. Several topical dosage forms such as aerosols, lotions, suppositories, tablets, gels, and creams have been proposed, although they are sometimes ineffective due to their poor penetration and rapid removal from the vaginal canal. For these reasons, the development of innovative drug delivery systems, able to remain in situ and release active agents for a prolonged period, is becoming more and more important. Among all, nanosystems such as liposomes, nanoparticles (NPs), and micelles with tunable surface properties, but also thermogelling nanocomposites, could be exploited to improve local drug delivery, biodistribution, retention, and uptake in vulvovaginal tissues. The aim of this review is to provide a survey of the variety of nanoplatforms developed for the vaginal delivery of antimicrobial agents. A concise summary of the most common vaginal infections and of the conventional therapies is also provided

Assessment of in‐situ gelling microemulsion systems upon temperature and dilution condition for corneal delivery of bevacizumab

Bevacizumab (BVZ), a recombinant humanized monoclonal antibody, has recently been proposed as a topical application in the treatment of anterior segment neovascularization; however, as there are some disadvantages in the administration of common eye-drops, ophthalmic topical drug delivery systems are under study to improve the precorneal residence time, reducing the frequency of administration. In this work, oil-in-water and water-in-oil BVZ-loaded microemulsions are developed, able to increase their viscosity, either by the formation of a liquid-crystalline structure upon aqueous dilution, thanks to the presence of Epikuron® 200 and polysorbate 80, or by body-temperature-induced jellification for the presence of Pluronic® F127 aqueous solution as an external phase. In oil-in-water microemulsion, hydrophobic ion pairs of BVZ were also prepared, and their incorporation was determined by release studies. Microemulsions were characterized for rheological behavior, corneal opacity, in vitro corneal permeation, and adhesion properties. The studied microemulsions were able to incorporate BVZ (from 1.25 to 1.6 mg/mL), which maintained dose-dependent activity on retinal pigment epithelial ARPE-19 cell lines. BVZ loaded in microemulsions permeated the excised cornea easier (0.76–1.56% BVZ diffused, 4–20% BVZ accumulated) than BVZ commercial solution (0.4% BVZ diffused, 5% accumulated) and only a mild irritation effect on the excised cornea was observed. The good adhesion properties as well the increased viscosity after application, under conditions that mimic the corneal environment (from 1 × 103 to more than 100 × 103 mPa·s), might prolong precorneal residence time, proving these systems could be excellent topical BVZ release systems

Nanoparticles Based on Fructose and Alkaly-Earth Halogenides with Second Harmonic Generation properties for applications as bio-sensors and for Radiotherapy

In recent years, some Metal Organic Frameworks with Second Harmonic Generation (SHG) properties, based on fructose and alkali-earth alogenides, were investigated to understand the effect of cation size and anion polarizability on crucial quantities correlated to the non-linear optical (NLO) response, such as hyperpolarizability and optical susceptibility [1,2]. The compounds studied are interesting for biomedicine applications, as they combine high biocompatibility, due to their non-toxic components, and significant SH emission, that can permit exploitation for in vitro bio-imaging. Right now, a possible application in radiotherapy is under investigation. To these purposes we synthetized nanoparticles of some MOFs, based on fructose and SrX2 salts (X=Cl, I). The compounds were characterized by single-crystal and powder XRD, IR and RAMAN spectroscopy and the second-order susceptibility were estimated from theoretical calculations, both in vacuo and in the solid state. Furthermore, we attempted to assess the reduction of the SH intensity for small quantities of nano-crystals, in order to ascertain the possibility of applications in biological systems. The nanoparticles were encapsulated in a phospholipidic shell and preliminary activity studies on target cells are in progress. [1] D. Marabello, P. Antoniotti, P. Benzi, C. Canepa, E. Diana, L. Operti, L. Mortati, M. P. Sassi J. Mater. Sci., 2015, 50 (12), 4330- 4341 [2] D. Marabello, P. Antoniotti, P. Benzi, C. Canepa, L. Mortati, M. P. Sassi Acta Cryst. B, accepte

The calming effect of a new wearable device during the anticipation of public speech

We assessed the calming effect of doppel, a wearable device that delivers heartbeat-like tactile stimulation on the wrist. We tested whether the use of doppel would have a calming effect on physiological arousal and subjective reports of state anxiety during the anticipation of public speech, a validated experimental task that is known to induce anxiety. Two groups of participants were tested in a single-blind design. Both groups wore the device on their wrist during the anticipation of public speech, and were given the cover story that the device was measuring blood pressure. For only one group, the device was turned on and delivered a slow heartbeat-like vibration. Participants in the doppel active condition displayed lower increases in skin conductance responses relative to baseline and reported lower anxiety levels compared to the control group. Therefore, the presence, as opposed to its absence, of a slow rhythm, which in the present study was instantiated as an auxiliary slow heartbeat delivered through doppel, had a significant calming effect on physiological arousal and subjective experience during a socially stressful situation. This finding is discussed in relation to past research on responses and entrainment to rhythms, and their effects on arousal and mood

Metabolic network alterations as a supportive biomarker in dementia with Lewy bodies with preserved dopamine transmission

Purpose Metabolic network analysis of FDG-PET utilizes an index of inter-regional correlation of resting state glucose metabolism and has been proven to provide complementary information regarding the disease process in parkinsonian syndromes. The goals of this study were (i) to evaluate pattern similarities of glucose metabolism and network connectivity in dementia with Lewy bodies (DLB) subjects with subthreshold dopaminergic loss compared to advanced disease stages and to (ii) investigate metabolic network alterations of FDG-PET for discrimination of patients with early DLB from other neurodegenerative disorders (Alzheimer’s disease, Parkinson’s disease, multiple system atrophy) at individual patient level via principal component analysis (PCA). Methods FDG-PETs of subjects with probable or possible DLB (n = 22) without significant dopamine deficiency (z-score < 2 in putamen binding loss on DaT-SPECT compared to healthy controls (HC)) were scaled by global-mean, prior to volume-of-interest-based analyses of relative glucose metabolism. Single region metabolic changes and network connectivity changes were compared against HC (n = 23) and against DLB subjects with significant dopamine deficiency (n = 86). PCA was applied to test discrimination of patients with DLB from disease controls (n = 101) at individual patient level. Results Similar patterns of hypo- (parietal- and occipital cortex) and hypermetabolism (basal ganglia, limbic system, motor cortices) were observed in DLB patients with and without significant dopamine deficiency when compared to HC. Metabolic connectivity alterations correlated between DLB patients with and without significant dopamine deficiency (R2 = 0.597, p < 0.01). A PCA trained by DLB patients with dopamine deficiency and HC discriminated DLB patients without significant dopaminergic loss from other neurodegenerative parkinsonian disorders at individual patient level (area-under-the-curve (AUC): 0.912). Conclusion Disease-specific patterns of altered glucose metabolism and altered metabolic networks are present in DLB subjects without significant dopaminergic loss. Metabolic network alterations in FDG-PET can act as a supporting biomarker in the subgroup of DLB patients without significant dopaminergic loss at symptoms onset

Medieval wooden sculpture in Sweden ; vol. I : Attitudes to the heritage ; vol. V : The Museum Collection-Plates

Salet Francis. Medieval wooden sculpture in Sweden ; vol. I : Attitudes to the heritage ; vol. V : The Museum Collection-Plates. In: Bulletin Monumental, tome 123, n°3, année 1965. pp. 264-265