Rapamycin-loaded polymeric nanoparticles as an advanced formulation for macrophage targeting in atherosclerosis

Recently, rapamycin (Rapa) represents a potential drug treatment to induce regression of atherosclerotic plaques; however, its use requires site-specific accumulation in the vessels involved in the formation of the plaques to avoid the systemic effects resulting from its indiscriminate biodistribution. In this work, a stable pharmaceutical formulation for Rapa was realized as a dried powder to be dispersed extemporaneously before administration. The latter was constituted by man-nitol (Man) as an excipient and a Rapa-loaded polymeric nanoparticle carrier. These nanoparticles were obtained by nanoprecipitation and using as a starting polymeric material a polycaprolactone (PCL)/α,β-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) graft copolymer. To obtain nanoparti-cles targeted to macrophages, an oxidized phospholipid with a high affinity for the CD36 receptor of macrophages, the 1-(palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine (KOdia-PC), was added to the starting organic phase. The chemical–physical and technological characterization of the obtained nanoparticles demonstrated that: both the drug loading (DL%) and the entrapment efficiency (EE%) entrapped drug are high; the entrapped drug is in the amorphous state, protected from degradation and slowly released from the polymeric matrix; and the KOdia-PC is on the nanoparticle surface (KP-Nano). The biological characterization demonstrated that both systems are quickly internalized by macrophages while maintaining the activity of the drug. In vitro studies demonstrated that the effect of KP-Nano Rapa-loaded, in reducing the amount of the Phospo-Ser757-ULK1 protein through the inhibition of the mammalian target of rapamycin (mTOR), is comparable to that of the free drug

Mpeg-plga nanoparticles labelled with loaded or conjugated rhodamine-b for potential nose-to-brain delivery

Nowdays, neurodegenerative diseases represent a great challenge from both the therapeutic and diagnostic points of view. Indeed, several physiological barriers of the body, including the blood brain barrier (BBB), nasal, dermal, and intestinal barriers, interpose between the development of new drugs and their effective administration to reach the target organ or target cells at therapeutic concentrations. Currently, the nose-to-brain delivery with nanoformulations specifically designed for intranasal administration is a strategy widely investigated with the goal to reach the brain while bypassing the BBB. To produce nanosystems suitable to study both in vitro and/or in vivo cells trafficking for potential nose-to-brain delivery route, we prepared and characterized two types of fluorescent poly(ethylene glycol)-methyl-ether-block-poly(lactide-co-glycolide) (PLGA\u2013PEG) nanoparticles (PNPs), i.e., Rhodamine B (RhB) dye loaded-and grafted-PNPs, respectively. The latter were produced by blending into the PLGA\u2013PEG matrix a RhB-labeled polyaspartamide/polylactide graft copolymer to ensure a stable fluorescence during the time of analysis. Photon correlation spectroscopy (PCS), UV-visible (UV-vis) spectroscopies, differential scanning calorimetry (DSC), atomic force microscopy (AFM) were used to characterize the RhB-loaded and RhB-grafted PNPs. To assess their potential use for brain targeting, cytotoxicity tests were carried out on olfactory ensheathing cells (OECs) and neuron-like differentiated PC12 cells. Both PNP types showed mean sizes suitable for nose-to-brain delivery (<200 nm, PDI < 0.3) and were not cytotoxic toward OECs in the concentration range tested, while a reduction in the viability on PC12 cells was found when higher concentrations of nanomedicines were used. Both the RhB-labelled NPs are suitable drug carrier models for exploring cellular trafficking in nose-to-brain delivery for short-time or long-term studies

Nanostructured Lipid Carriers-Containing Anticancer Compounds: Preparation, Characterization, and Cytotoxicity Studies

This article describes the development of nanostructured lipid carriers (NLC) as colloidal carriers for two antitumor compounds that possess a remarkable antineoplastic activity. But their limited stability and low solubility in water could give a very low parenteral bioavailability. Results revealed an enhancement of the cytotoxicity effect of drug-loaded NLC on human prostate cancer (PC-3) and human hepatocellular carcinoma (HuH-6, HuH-7) cell lines with respect to that of both free drugs. Results of characterization studies strongly support the potential application of these drugs-loaded NLC as prolonged delivery systems for lipophilic drugs by several administration routes, in particular for intravenous administration

Evidence of abnormal scalar timing property in alexithymia

: Evidence suggests that incidental modulation of affective states affects the ability to keep track of time. Alexithymia represents an ideal condition to further address the emotion-time processing link, as it refers to a trait characterized by a deficit of affective processing. 31 healthy participants completed an online version of the TAS-20 scale, which measures alexithymia, and a time reproduction task of visual stimuli related to positive (i.e., happiness) and negative (i.e., anger) facial expressions. Results documented a positive correlation between TAS-20 score and the variability in reproducing sub-second durations of the anger expression stimuli We also found an overestimation of sub-second durations of non-affective expressions in borderline/alexithymic participants. Finally, in line with the literature, we confirmed the overall tendency to overestimate the duration of anger expression stimuli. These findings, which can be interpreted in terms of abnormal scalar timing property in alexithymia, expand previous investigations linking this personality trait with abnormal processing of negative emotions. The evidence that alexithymia predicts the reproduction variability of sub-second durations of negative affective stimuli corroborates previous neuroimaging studies documenting cerebellar deficits in these individuals

Application of technological protocols on an industrial scale to improve Seville-style table olive production in Italy and Spain

Improving the fermentation performance of starter strains used in the fermentation of table olives is a biotechnological solution of current interest to improve the quality characteristics of the final product. The aim of this study was to evaluate the use of Lactiplantibacillus pentosus OM13 as a starter culture for the fermentation of Seville-type table olives in two different production areas: Italy and Spain. The starter strain L. pentosus OM13 was inoculated into two different table olive varieties: Nocellara del Belice in Italy and Manzanilla in Spain. Lactiplantibacillus plantarum Vege-Start 60 was used as a commercial control, while an additional control pro- duction was carried out by spontaneous fermentation. The industrial productions consisted of three different protocols, differing in the type of nutrient and the presence/absence of acclimatisation of the starter strain. All trials were subjected to microbiological monitoring, evaluation of acidification dynamics and sensory analysis of the final product. After 90 days, the pH reached values below 5 in the different treatments. The LAB reached microbial loads varying between 6.5 and 8.7 log CFU/mL throughout the monitoring period. The microbial populations of spoilage and/or potential pathogenic microorganisms were variable depending on the microbial group monitored. However, after 12 days of fermentation, Enterobacteriaceae showed values below the detection limit. In contrast, a fluctuating trend was observed for yeasts, Pseudomonadaceae and Staphylococcaceae. Sensory analyses showed variable differences depending on the technological protocol used. Table olives ob- tained with L. pentosus OM13 in the presence of nutrient, activator and acclimatisation period achieved higher overall acceptability values compared to the other trials. The use of adjuvants (nutrients and activators) is a strategy used in the production of table olives fermented with L. pentosus OM13 to improve the sensory char- acteristics of table olives

Monitoring commercial starter culture development in presence of red grape pomace powder to produce polyphenol-enriched fresh ovine cheeses at industrial scale level

Red grape Nero d'Avola cultivar grape pomace powder (GPP) was applied during fresh ovine cheese production in order to increase polyphenol content. Before cheeses were produced, the bacteria of a freeze-dried commercial starter culture were isolated and tested in vitro against GPP. Two dominant strains, both resistant to GPP, were identified. Thestarter culture was inoculated in pasteurized ewe's milk and the curd was divided into two bulks, one added with 1% (w/w) GPP and another one GPP-free. GPP did not influence the starter culture development, since lactic acid bacteria (LAB) counts were 109 CFU/g in both cheeses at 30 d. To exclude the interference of indigenous LAB, the pasteurized milk was analyzed, and several colonies of presumptive LAB were isolated, purified and typed. Four strains were allotted into Enterococcus and Lacticaseibacillus genera. The direct comparison of the polymorphic profiles of cheese bacteria evidenced the dominance of the starter culture over milk LAB. The addition of GPP increased cheese total phenolic compounds by 0.42 g GAE/kg. Sensory evaluation indicated that GPP-enriched cheese was well appreciated by the judges, providing evidence that GPP is a suitable substrate to increase the availability of total phenolic content in fresh ovine cheese

Hippocampal and Amygdalar Volumes Changes in Drug Addicts: A Preliminary Study

Oral comunication for American Society of Neuroradiology 45th Annual Meeting. Chicago, June 9-14 200

Twenty years of experience in juvenile nasopharyngeal angiofibroma (JNA) preoperative endovascular embolization: An effective procedure with a low complications rate

Juvenile nasopharyngeal angiofibroma (JNA) is a benign tumor of the nasal cavity that predominantly affects young boys. Surgical removal remains the gold standard for the management of this disease. Preoperative intra-arterial embolization (PIAE) is useful for reductions in intraoperative blood loss and surgical complications. In our series of 79 patients who underwent preoperative embolization from 1999 to 2020, demographics, procedural aspects, surgical management and follow-up outcome were analyzed. Embolization was performed in a similar fashion for all patients, with a superselective microcatheterization of external carotid artery (ECA) feeders and an injection of polyvinyl alcohol (PVA) particles, followed, in some cases, by the deployment of coils. Procedural success was reached in 100% of cases, with no complications such as bleeding or thromboembolic occlusion, and surgical intraoperative blood loss was significantly decreased. In conclusion, PIAE is a safe and effective technique in JNA treatment, minimizing intraoperative bleeding