21 research outputs found

    Enhanced Anti-Herpetic Activity of Valacyclovir Loaded in Sulfobutyl-ether-β-cyclodextrin-decorated Chitosan Nanodroplets

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    Valacyclovir (VACV) was developed as a prodrug of the most common anti-herpetic drug Acyclovir (ACV), aiming to enhance its bioavailability. Nevertheless, prolonged VACV oral treatment may lead to the development of important side effects. Nanotechnology-based formulations for vaginal administration represent a promising approach to increase the concentration of the drug at the site of infection, limiting systemic drug exposure and reducing systemic toxicity. In this study, VACV-loaded nanodroplet (ND) formulations, optimized for vaginal delivery, were designed. Cell-based assays were then carried out to evaluate the antiviral activity of VACV loaded in the ND system. The chitosan-shelled ND exhibited an average diameter of about 400 nm and a VACV encapsulation efficiency of approximately 91% and was characterized by a prolonged and sustained release of VACV. Moreover, a modification of chitosan shell with an anionic cyclodextrin, sulfobutyl ether β-cyclodextrin (SBEβCD), as a physical cross-linker, increased the stability and mucoadhesion capability of the nanosystem. Biological experiments showed that SBEβCD-chitosan NDs enhanced VACV antiviral activity against the herpes simplex viruses type 1 and 2, most likely due to the long-term controlled release of VACV loaded in the ND and an improved delivery of the drug in sub-cellular compartments

    Long-lasting neutralizing antibodies and T cell response after the third dose of mRNA anti-SARS-CoV-2 vaccine in multiple sclerosis

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    Background and objectivesLong lasting immune response to anti-SARS-CoV-2 vaccination in people with Multiple Sclerosis (pwMS) is still largely unexplored. Our study aimed at evaluating the persistence of the elicited amount of neutralizing antibodies (Ab), their activity and T cell response after three doses of anti-SARS-CoV-2 vaccine in pwMS.MethodsWe performed a prospective observational study in pwMS undergoing SARS-CoV-2 mRNA vaccinations. Anti-Region Binding Domain (anti-RBD) of the spike (S) protein immunoglobulin G (IgG) titers were measured by ELISA. The neutralization efficacy of collected sera was measured by SARS-CoV-2 pseudovirion-based neutralization assay. The frequency of Spike-specific IFNγ-producing CD4+ and CD8+ T cells was measured by stimulating Peripheral Blood Mononuclear Cells (PBMCs) with a pool of peptides covering the complete protein coding sequence of the SARS-CoV-2 S.ResultsBlood samples from 70 pwMS (11 untreated pwMS, 11 under dimethyl fumarate, 9 under interferon-γ, 6 under alemtuzumab, 8 under cladribine, 12 under fingolimod and 13 under ocrelizumab) and 24 healthy donors were collected before and up to six months after three vaccine doses. Overall, anti-SARS-CoV-2 mRNA vaccine elicited comparable levels of anti-RBD IgGs, neutralizing activity and anti-S T cell response both in untreated, treated pwMS and HD that last six months after vaccination. An exception was represented by ocrelizumab-treated pwMS that showed reduced levels of IgGs (p<0.0001) and a neutralizing activity under the limit of detection (p<0.001) compared to untreated pwMS. Considering the occurrence of a SARS-CoV-2 infection after vaccination, the Ab neutralizing efficacy (p=0.04), as well as CD4+ (p=0.016) and CD8+ (p=0.04) S-specific T cells, increased in treated COVID+ pwMS compared to uninfected treated pwMS at 6 months after vaccination.DiscussionOur follow-up provides a detailed evaluation of Ab, especially in terms of neutralizing activity, and T cell responses after anti-SARS-CoV-2 vaccination in MS context, over time, considering a wide number of therapies, and eventually breakthrough infection. Altogether, our observations highlight the vaccine response data to current protocols in pwMS and underline the necessity to carefully follow-up anti-CD20- treated patients for higher risk of breakthrough infections. Our study may provide useful information to refine future vaccination strategies in pwMS

    Heating of metallic biliary stents during magnetic hyperthermia of patients with pancreatic ductal adenocarcinoma: an in silico study.

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    To investigate the eddy current heating that occurs in metallic biliary stents during magnetic hyperthermia treatments and to assess whether these implants should continue to be an exclusion criterion for potential patients. Computer simulations were run on stent heating during the hyperthermia treatment of local pancreatic tumors (5-15 mT fields at 300 kHz for 30 min), considering factors such as wire diameter, type of stent alloy, and field orientation. Maxwell's equations were solved numerically in a bile duct model, including the secondary field produced by the stents. The heat exchange problem was solved through a modified version of the Pennes' bioheat equation assuming a temperature dependency of blood perfusion and metabolic heat. The choice of alloy has a large impact on the stent heating, preferring those having a lower electrical conductivity. Only for low field intensities (5 mT) and for some of the bile duct tissue layers the produced heating can be considered safe. The orientation of the applied field with respect to the stent wires can give rise to the onset of regions with different heating levels depending on the shape that the stent has finally adopted according to the body's posture. Bile helps to partially dissipate the heat that is generated in the lumen of the bile duct, but not at a sufficient rate. The safety of patients with pancreatic cancer wearing metallic biliary stents during magnetic hyperthermia treatments cannot be fully assured under the most common treatment parameters

    Dataset from "In silico assessment of collateral eddy current heating in biocompatible implants subjected to magnetic hyperthermia treatments"

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    This dataset from the publication entitled "Dataset from "In silico assessment of collateral eddy current heating in biocompatible implants subjected to magnetic hyperthermia treatments" contains simulated data of magnetic hyperthermia treatments for three different indications: colorectal cancer, prostate cancer and head & neck cancer. Since the aim of the study is to evaluate the risk of thermal damage caused by the collateral heating of two common types of passive prostheses (hip and dental implants), eddy currents induced in these implants upon interacting with the externally applied ac field during treatment have been computed for all the evaluated regions. Two different alloys for the implants have been considered for each case as well: Ti6Al4V and CoCrMo. At the same time, besides temperature, the specific abosorption rate (SAR) have been also computed to work out the energy deposition in tissues. Calculations have been carried out using a het exchange model with and without thermoregulation. log-log SAR vs T plots have been obtained and proposed as a quick means to pre-check treatment feasibility in each patient. These graphs are thought to be included in treatment planning prior to the clinical procedure. Other parameters taken into account have been the treatment time (5 and 30 minutes), and the maximum tolerable temperature threshold (1 or 5 ºC, as indicated by the ICNIRP commission), all for three main types of tissues, namely fat, bone and muscle. Each tissue have been simulated using three different field intensities (5, 10 and 15 mT). The field frequency has been 300 kHz in all cases. The files "Dataset_description.doc" and "file_scheme.txt" contain the structure and description of the files that make up the dataset. UPDATES FROM PREVIOUS VERSIONS: simulations of the dental implant without thermoregulation have been added
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