Exploring the immunomodulatory properties of glucan particles in human primary cells.

The immunomodulatory properties of β-glucans have sparked interest among various medical fields. As vaccine adjuvants, glucan particles offer additional advantages as antigen delivery systems. This study reported the immunomodulatory properties of glucan particles with different size and chemical composition.

Hospitalizations in Brazil according to National Health Survey estimates, 2013 and 2019.

Objective: To compare the profile and prevalence of hospitalizations in Brazil based on estimates from the National Health Survey (PNS), 2013 and 2019.

Methods: A cross-sectional study that used data from the 2013 PNS and the 2019 PNS. The outcome was having been hospitalized for 24 hours or more in the last 12 months.

Endotoxin contamination of nanoparticle formulations: A concern in vaccine adjuvant mechanistic studies.

The increasing awareness of endotoxin contamination has raised important questions during the study of the mechanism of action of the vaccine adjuvants. The endotoxins or lipopolysaccharides (LPS) can contaminate vaccine formulations contributing to result misinterpretations of the in vitro and in vivo studies. In this short communication, we considered the suitability of the Limulus amebocyte lysate (LAL) assay to quantify chitosan (Chit) nanoparticle (NP) endotoxin contamination to use them in a comparative in vitro immunotoxicology study using both LPS-free (LF) and non-LF Chit NPs.

Unravelling the Immunotoxicity of Polycaprolactone Nanoparticles-Effects of Polymer Molecular Weight, Hydrolysis, and Blends.

Poly-ε-caprolactone (PCL) is a biodegradable polyester that has FDA and CE approval as a medical device. Nonetheless, the lack of toxicity exhibited by the polymer cannot be extrapolated to its nanomaterial conformation. Despite PCL-based NPs being widely studied in the biomedical field for their advantages as controlled drug delivery systems, little data describe PCL NPs' toxicity, particularly immunotoxicity.

Chitosan-coated PLGA nanoparticles for the nasal delivery of ropinirole hydrochloride: In vitro and ex vivo evaluation of efficacy and safety.

Nose-to-brain delivery is an attractive route for direct drug delivery to the central nervous system (CNS), avoiding hepatic first-pass metabolism and solving blood-brain barrier passage issues. Therefore, the aim of the present study was the development of PLGA and PLGA/chitosan (chit) nanoparticles (NPs) with mucoadhesive properties, able to encapsulate ropinirole hydrochloride (RH), an anti-Parkinsonian dopaminergic agonist, and suitable to promote RH delivery across the nasal mucosa. NPs produced by nanoprecipitation showed spherical shape and a mean average size of 98.

A Methodological Safe-by-Design Approach for the Development of Nanomedicines.

Safe-by-Design (SbD) concepts foresee the risk identification and reduction as well as uncertainties regarding human health and environmental safety in early stages of product development. The EU's NANoREG project and further on the H2020 ProSafe initiative, NanoReg2, and CALIBRATE projects have developed a general SbD approach for nanotechnologies (e.g.

Chitosan Nanoparticles: Shedding Light on Immunotoxicity and Hemocompatibility.

Nanoparticles (NPs) assumed an important role in the area of drug delivery. Despite the number of studies including NPs are growing over the last years, their side effects on the immune system are often ignored or omitted. One of the most studied polymers in the nano based drug delivery system field is chitosan (Chit).

Safe-by-Design of Glucan Nanoparticles: Size Matters When Assessing the Immunotoxicity.

Glucan (from ) is a polymer composed of β-1,3-linked glucose residues, and it has been addressed in different medical fields, namely in nanotechnology, as a vaccine or a drug delivery system. However, due to their small size, nanomaterials may present new risks and uncertainties. Thus, this work aims to describe the production of glucan nanoparticles (NPs) with two different sizes, and to evaluate the influence of the NPs size on immunotoxicity.

Hazard Assessment of Polymeric Nanobiomaterials for Drug Delivery: What Can We Learn From Literature So Far.

The physicochemical properties of nanobiomaterials, such as their small size and high surface area ratio, make them attractive, novel drug-carriers, with increased cellular interaction and increased permeation through several biological barriers. However, these same properties hinder any extrapolation of knowledge from the toxicity of their raw material. Though, as suggested by the Safe-by-Design (SbD) concept, the hazard assessment should be the starting point for the formulation development.

Poly(D,L-Lactic Acid) Nanoparticle Size Reduction Increases Its Immunotoxicity.

Polylactic acid (PLA), a biodegradable and biocompatible polymer produced from renewable resources, has been widely used as a nanoparticulate platform for antigen and drug delivery. Despite generally regarded as safe, its immunotoxicological profile, when used as a polymeric nanoparticle (NP), is not well-documented. Thus, this study intends to address this gap, by evaluating the toxicity of two different sized PLA NPs (PLA NPs and PLA NPs), produced by two nanoprecipitation methods and extensively characterized regarding their physicochemical properties in experimental conditions.

Surgical Excision of an Adrenal Neuroblastoma in a Dog.

A 11-month-old, intact male, Rhodesian Ridgeback was presented to the Veterinary Teaching Hospital with signs of inappetence, lethargy, and abdominal pain for 3 days. A large and well-defined abdominal retroperitoneal mass, related with the left kidney, at the expected location of the adrenal gland, was revealed by radiography, ultrasound, and computed tomography. The mass extended caudally to the iliac artery bifurcation, compressing the aorta, caudal vena cava, and both kidneys.

Radiographic Reference Values for the Cardiac Silhouette in Bonelli's Eagle ().

Radiographs are an important diagnostic tool available in wildlife hospitals to evaluate the size of the avian heart. Despite the large variety wild birds in the Iberian peninsula, clinical studies addressing these species are lacking. To establish reference values for cardiac size in the Bonelli's eagle (), ventrodorsal radiographs of 20 healthy birds were obtained, and the width of the cardiac silhouette, sternum, thorax, coracoid, and hepatic silhouette were measured.

Optimization of Chitosan-α-casein Nanoparticles for Improved Gene Delivery: Characterization, Stability, and Transfection Efficiency.

Among non-viral vectors, the cationic polymer chitosan has gained attention as a gene delivery system. We hypothesized that the addition of casein into the nanoparticle's structure would facilitate a proper gene transfer. The work herein presented aimed to optimize the production method of chitosan-casein nanoparticles (ChiCas NPs) and to test their ability as a gene delivery system.

Chitosan Plus Compound 48/80: Formulation and Preliminary Evaluation as a Hepatitis B Vaccine Adjuvant.

Current vaccine research is mostly based on subunit antigens. Despite the better toxicity profile of these antigens they are often poorly immunogenic, so adjuvant association has been explored as a strategy to obtain a potent vaccine formulation. Recently, mast cell activators were recognized as a new class of vaccine adjuvants capable of potentiating mucosal and systemic immune responses.

Exosomes as adjuvants for the recombinant hepatitis B antigen: First report.

Over the past few years, exosomes, a class of extracellular vesicles (EVs), have emerged as key players for inter-cellular communication ultimately modulating the behavior of target cells with countless outcomes. Nevertheless, the potential role of exosomes as vaccine adjuvants remains largely unexplored. Herein, we hypothesized that exosomes derived from immune cells may have an immunostimulatory effect and could constitute a good target towards the development of new fine-tuned vaccine adjuvants.

Chitosan:β-glucan particles as a new adjuvant for the hepatitis B antigen.

The development of new vaccine adjuvants is urgently needed not only to enable new routes of vaccine administration but mostly to go beyond protective humoral immunity, often insufficient to fight infectious diseases. The association of two or more immunopotentiators or mimicking pathogen physicochemical properties are strategies that can favor powerful and more balanced Th1/Th2 immune responses. Therefore, the present work aimed to combine both chitosan and β-glucan biopolymers in the same particle, preferably with surface β-glucan localization to simulate the cell wall of some pathogens and to stimulate the immune cells expressing the Dectin-1 receptor.

Adjuvant Activity of Poly-ε-caprolactone/Chitosan Nanoparticles Characterized by Mast Cell Activation and IFN-γ and IL-17 Production.

Polymeric nanoparticles (NPs) are extremely attractive vaccine adjuvants, able to promote antigen delivery and in some instances, exert intrinsic immunostimulatory properties that enhance antigen specific humoral and cellular immune responses. The poly-ε-caprolactone (PCL)/chitosan NPs were designed with the aim of being able to combine the properties of the 2 polymers in the preparation of an adjuvant for the hepatitis B surface antigen (HBsAg). This article reports important results of an in vitro mechanistic study and immunization studies with HBsAg associated with different concentrations of the nanoparticles.

Oral hepatitis B vaccine: chitosan or glucan based delivery systems for efficient HBsAg immunization following subcutaneous priming.

The World Health Organization encourages "the development of oral formulations to simplify their transport, storage and administration in poor countries", and to "facilitate an effective immunization program to prevent sexually transmitted hepatitis B". Thus, two distinct and promising delivery systems were developed: recombinant hepatitis B surface antigen (HBsAg) encapsulated into alginate-coated chitosan particles (AlgChiPs) and into glucan particles (GPs) mainly composed of β-1,3-d-glucan. In vitro preliminary studies showed that both could be internalized by peripheral blood mononuclear cells and murine Peyer's patches, an imperative aspect regarding oral immunization.

Poly-ϵ-caprolactone/chitosan nanoparticles provide strong adjuvant effect for hepatitis B antigen.

Aim: This work aims to investigate the adjuvant effect of poly-ϵ-caprolactone/chitosan nanoparticles (NPs) for hepatitis B surface antigen (HBsAg) and the plasmid DNA encoding HBsAg (pRC/CMV-HBs).

Methods: Both antigens were adsorbed onto preformed NPs. Vaccination studies were performed in C57BL/6 mice.

The Inclusion of Chitosan in Poly-ε-caprolactone Nanoparticles: Impact on the Delivery System Characteristics and on the Adsorbed Ovalbumin Secondary Structure.

This report extensively explores the benefits of including chitosan into poly-ε-caprolactone (PCL) nanoparticles (NPs) to obtain an improved protein/antigen delivery system. Blend NPs (PCL/chitosan NPs) showed improved protein adsorption efficacy (84%) in low shear stress and aqueous environment, suggesting that a synergistic effect between PCL hydrophobic nature and the positive charges of chitosan present at the particle surface was responsible for protein interaction. Additionally, thermal analysis suggested the blend NPs were more stable than the isolated polymers and cytotoxicity assays in a primary cell culture revealed chitosan inclusion in PCL NPs reduced the toxicity of the delivery system.

Poly-ε-caprolactone/Chitosan and Chitosan Particles: Two Recombinant Antigen Delivery Systems for Intranasal Vaccination.

Several evidences converge on the idea that among the mucosal administration routes, the nasal mucosa is the most attractive site for the delivery of vaccines. Mucoadhesive particulate adjuvants should be able to increase the residence time of antigens in nasal cavity in order to increase their probability of being taken up by nasopharynx-associated lymphoid tissue (NALT) cells and subsequently to initiate the innate and adaptive immune response. Focusing on chitosan, a mucoadhesive biopolymer, we describe in this chapter a method to prepare antigen loaded chitosan nanoparticles and a second method to prepare antigen loaded poly-ε-caprolactone/chitosan nanoparticles.

Immune response elicited by an intranasally delivered HBsAg low-dose adsorbed to poly-ε-caprolactone based nanoparticles.

Among new strategies to increase hepatitis B virus (HBV) vaccination, especially in developing countries, the development of self-administered vaccines is considered one of the most valuable. Nasal vaccination using polymeric nanoparticles (NPs) constitutes a valid approach to this issue. In detail, poly-ε-caprolactone (PCL)/chitosan NPs present advantages as a mucosal vaccine delivery system: the high resistance of PCL against degradation in biological fluids and the mucoadhesive and immunostimulatory properties of chitosan.

Sonication-Assisted Layer-by-Layer Assembly for Low Solubility Drug Nanoformulation.

Sonication-assisted layer-by-layer (LbL) self-assembly is a nanoencapsulation technique based on the alternate adsorption of oppositely charged polyelectrolytes, enabling the encapsulation of low solubility drugs. In this work, a top-down LbL technique was performed using a washless approach and ibuprofen (IBF) as a model class II drug. For each saturated layer deposition, polyelectrolyte concentration was determined by titration curves.

A comparison of the Beers and STOPP criteria for identifying the use of potentially inappropriate medications among elderly patients in primary care.

Rationale, Aims And Objectives: Explicit criteria for evaluating the appropriateness of medication use among the elderly have been extensively employed in several countries. The aim of the current study was to assess and characterize the prevalence of potentially inappropriate medications (PIMs) according to the Screening Tool of Older People's Prescriptions (STOPP) criteria and compare these data with the 2012 Beers criteria.

Methods: A prospective survey of the medications used by elderly patients was performed.

Effectiveness of rotavirus vaccine against hospitalized rotavirus diarrhea: A case-control study.

Rotavirus is one of the leading cause of hospitalization and outpatients visits among children under five years. This study evaluated overall and genotype-specific vaccine effectiveness of oral monovalent rotavirus vaccine (G1P[8] strain) in preventing hospital admission of Brazilian children with rotavirus acute diarrhea. A hospital based case-control study was conducted in five Regions of Brazil using the National Rotavirus Acute Diarrhea Surveillance System from July 2008 to August 2011.