Investigation of blood-brain barrier penetration and pharmacokinetics of a new formulation of cyanide antidote dimethyl trisulfide.

Objective: During cyanide poisoning, the rescue of vital organs like the brain is urgent. However, due to the presence of the blood-brain barrier (BBB), the currently available cyanide antidotes cannot reach the brain. Dimethyl trisulfide (DMTS) is a potent cyanide antidote and has excellent BBB permeability.

,-dimethyltryptamine mitigates experimental stroke by stabilizing the blood-brain barrier and reducing neuroinflammation.

,-dimethyltryptamine (DMT) is a psychoactive molecule present in the human brain. DMT is under clinical evaluation as a neuroprotective agent in poststroke recovery. Yet, its mechanism of action remains poorly understood.

Sijunzi Decoction treatment improved depression with qi deficiency/fatigue in the strain-dependent manner, involved in anti-inflammation in the hippocampus and muscles.

Ethnopharmacological Relevance: In the traditional Chinese medicine (TCM) clinic, qi deficiency is a common syndrome pattern in major depressive disorder (MDD). Sijunzi decoction (SJZD), a classic muti-herbal formula to replenish qi and nourish blood, is widely used to treat qi deficiency syndrome. The symptoms of qi deficiency are very similar to fatigue.

The impact of the novel σ receptor ligand (S)-L1 on brain endothelial cells and cerebrovascular reactivity challenged by ischemia.

Intracellular sigma-1 receptors (σ receptors) have a versatile function through the regulation of lipid rafts, neuroreceptors and ion channels, and can influence signal transduction and neuronal plasticity. Since decreased activity of σ receptors is a common pathological feature in the early stages of many neurological diseases, σ receptor agonists may represent a promising therapeutic tool for the treatment of these disorders. In this study, we aimed to comprehensively investigate the potential protective effects of the novel synthetic σ receptor agonist (S)-L1 against endothelial endoplasmic reticulum (ER) stress and cerebral ischemia.

Mannitol-leucine synergy in nanocrystal agglomerates for enhanced systemic delivery of inhaled ketoprofen: Pharmacokinetics and safety in ovalbumin-sensitized rats.

Pulmonary administration offers a promising needle-free approach for systemic delivery of nonsteroidal anti-inflammatory drugs (NSAIDs), improving bioavailability and reducing required doses. While mannitol and leucine are widely used in inhalation formulations, their potential to enhance systemic drug delivery via the pulmonary route remains largely unexplored. This study utilizes the nanocrystal agglomerates (NCAs) approach to develop an inhalable NSAID formulation, with ketoprofen (KTP) as a model drug.

Nicotinamide derivatives protect the blood-brain barrier against oxidative stress.

Nicotinamides play a crucial role in energy metabolism and maintenance of the redox homeostasis counteracting oxidative stress and elevated reactive oxidative species (ROS) in human cells. The levels of nicotinamides decline with age and are associated with various pathologies, including ones linked with the blood-brain barrier disorder. Therefore, the investigation of the bioactivity of synthetic nicotinamide derivates (NAs) and evaluation of their potential to protect the blood-brain barrier (BBB) from oxidative stress is emerging as an important new strategy.

PepH3-modified nanocarriers for delivery of therapeutics across the blood-brain barrier.

Background: Nanocarriers targeting the blood-brain barrier (BBB) are promising drug delivery systems to enhance the penetration of therapeutic molecules into the brain. Immunotherapy, particularly monoclonal antibodies designed to bind amyloid-beta peptides have become a promising strategy for Alzheimer's disease, but ensuring efficacy and safety is challenging and crucial for these therapies. Our aim was to develop an innovative nanocarriers conjugated with PepH3, a cationic peptide derived from Dengue virus type-2 capsid protein that crosses the BBB and acts as a shuttle peptide for the encapsulated single domain antibody (sdAb) recognizing Aβ oligomers.

Much More than Nutrients: The Protective Effects of Nutraceuticals on the Blood-Brain Barrier in Diseases.

The dysfunction of the blood-brain barrier (BBB) is well described in several diseases, and is considered a pathological factor in many neurological disorders. This review summarizes the most important groups of natural compounds, including alkaloids, flavonoids, anthocyanidines, carotenoids, lipids, and vitamins that were investigated for their potential protective effects on brain endothelium. The brain penetration of these compounds and their interaction with BBB efflux transporters and solute carriers are discussed.

Alanine and glutathione targeting of dopamine- or ibuprofen-coupled polypeptide nanocarriers increases both crossing and protective effects on a blood-brain barrier model.

Background: Targeting the blood-brain barrier (BBB) is a key step for effective brain delivery of nanocarriers. We have previously discovered that combinations of BBB nutrient transporter ligands alanine and glutathione (A-GSH), increase the permeability of vesicular and polypeptide nanocarriers containing model cargo across the BBB. Our aim was to investigate dopamine- and ibuprofen-coupled 3-armed poly(L-glutamic acid) nanocarriers targeted by A-GSH for transfer across a novel human co-culture model with induced BBB properties.

The effect of mucoadhesive polymers on ocular permeation of thermoresponsive in situ gel containing dexamethasone-cyclodextrin complex.

Dexamethasone (DXM) is a commonly used corticosteroid in the treatment of ocular inflammatory conditions that affect more and more people. The aim of this study was to evaluate the effect of the combination of hydroxypropyl-β-cyclodextrin (HPBCD), in situ gelling formulations, and other mucoadhesive polymers, i.e.

Antidepressant-induced membrane trafficking regulates blood-brain barrier permeability.

As the most prescribed psychotropic drugs in current medical practice, antidepressant drugs (ADs) of the selective serotonin reuptake inhibitor (SSRI) class represent prime candidates for drug repurposing. The mechanisms underlying their mode of action, however, remain unclear. Here, we show that common SSRIs and selected representatives of other AD classes bidirectionally regulate fluid-phase uptake at therapeutic concentrations and below.

17-Oxime ethers of oxidized ecdysteroid derivatives modulate oxidative stress in human brain endothelial cells and dose-dependently might protect or damage the blood-brain barrier.

20-Hydroxyecdysone and several of its oxidized derivatives exert cytoprotective effect in mammals including humans. Inspired by this bioactivity of ecdysteroids, in the current study it was our aim to prepare a set of sidechain-modified derivatives and to evaluate their potential to protect the blood-brain barrier (BBB) from oxidative stress. Six novel ecdysteroids, including an oxime and five oxime ethers, were obtained through regioselective synthesis from a sidechain-cleaved calonysterone derivative 2 and fully characterized by comprehensive NMR techniques revealing their complete 1H and 13C signal assignments.

Lab-on-a-chip models of the blood-brain barrier: evolution, problems, perspectives.

A great progress has been made in the development and use of lab-on-a-chip devices to model and study the blood-brain barrier (BBB) in the last decade. We present the main types of BBB-on-chip models and their use for the investigation of BBB physiology, drug and nanoparticle transport, toxicology and pathology. The selection of the appropriate cell types to be integrated into BBB-on-chip devices is discussed, as this greatly impacts the physiological relevance and translatability of findings.

Design, Optimization, and Application of a 3D-Printed Polymer Sample Introduction System for the ICP-MS Analysis of Nanoparticles and Cells.

Commonly used sample introduction systems for inductively coupled plasma mass spectrometry (ICP-MS) are generally not well-suited for single particle ICP-MS (spICP-MS) applications due to their high sample requirements and low efficiency. In this study, the first completely 3D-printed, polymer SIS was developed to facilitate spICP-MS analysis. The system is based on a microconcentric pneumatic nebulizer and a single-pass spray chamber with an additional sheath gas flow to further facilitate the transport of larger droplets or particles.

Nogo-A is secreted in extracellular vesicles, occurs in blood and can influence vascular permeability.

Nogo-A is a transmembrane protein with multiple functions in the central nervous system (CNS), including restriction of neurite growth and synaptic plasticity. Thus far, Nogo-A has been predominantly considered a cell contact-dependent ligand signaling via cell surface receptors. Here, we show that Nogo-A can be secreted by cultured cells of neuronal and glial origin in association with extracellular vesicles (EVs).

The Use of Sensors in Blood-Brain Barrier-on-a-Chip Devices: Current Practice and Future Directions.

The application of lab-on-a-chip technologies in in vitro cell culturing swiftly resulted in improved models of human organs compared to static culture insert-based ones. These chip devices provide controlled cell culture environments to mimic physiological functions and properties. Models of the blood-brain barrier (BBB) especially profited from this advanced technological approach.

Highly Oxidized Ecdysteroids from a Commercial Root Extract as Potent Blood-Brain Barrier Protective Agents.

Ecdysteroid-containing herbal extracts, commonly prepared from the roots of , are marketed worldwide as a "green" anabolic food supplement. Herein are reported the isolation and complete H and C NMR signal assignments of three new minor ecdysteroids (compounds -) from this extract. Compound was identified as a possible artifact that gradually forms through the autoxidation of calonysterone.

Targeting Human Endothelial Cells with Glutathione and Alanine Increases the Crossing of a Polypeptide Nanocarrier through a Blood-Brain Barrier Model and Entry to Human Brain Organoids.

Nanoparticles (NPs) are the focus of research efforts that aim to develop successful drug delivery systems for the brain. Polypeptide nanocarriers are versatile platforms and combine high functionality with good biocompatibility and biodegradability. The key to the efficient brain delivery of NPs is the specific targeting of cerebral endothelial cells that form the blood-brain barrier (BBB).

Soluplus® promotes efficient transport of meloxicam to the central nervous system via nasal administration.

In our present series of experiments, we investigated the nasal applicability of the previously developed Soluplus® - meloxicam polymeric micelle formulation. Utilizing the nasal drug investigations, moderately high mucoadhesion was experienced in nasal conditions which alongside the appropriate physicochemical properties in liquid state, contributed to rapid drug absorption through human RPMI 2650 cell line. Ex vivo studies also confirmed that higher nasal mucosal permeation could be expected with the polymeric micelle nanoformulation compared to a regular MEL suspension.

Effects of Hydroxypropyl-Beta-Cyclodextrin on Cultured Brain Endothelial Cells.

The application of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) in the treatment of the rare cholesterol and lipid storage disorder Niemann-Pick disease type C opened new perspectives in the development of an efficient therapy. Even if the systemic administration of HPBCD was found to be effective, its low permeability across the blood-brain barrier (BBB) limited the positive neurological effects. Nevertheless, the cellular interactions of HPBCD with brain capillary endothelial cells have not been investigated in detail.

Effects of sub-chronic, in vivo administration of sigma-1 receptor ligands on platelet and aortic arachidonate cascade in streptozotocin-induced diabetic rats.

Background: Diabetes mellitus is a chronic metabolic disorder which induces endothelial dysfunction and platelet activation. Eicosanoids produced from arachidonic acid regulate cellular and vascular functions. Sigma-1 receptors (S1R) are expressed in platelets and endothelial cells and S1R expression is protective in diabetes.

Distinct Uptake Routes Participate in Silver Nanoparticle Engulfment by Earthworm and Human Immune Cells.

The consequences of engineered silver nanoparticle (AgNP) exposure and cellular interaction with the immune system are poorly understood. The immunocytes of the earthworm are frequently applied in ecotoxicological studies and possess functional similarity to vertebrate macrophages. Hence, we characterized and compared the endocytosis mechanisms for the uptake of 75 nm AgNPs by earthworm coelomocytes, human THP-1 monocytes, and differentiated THP-1 (macrophage-like) cells.