The blood–brain barrier (BBB) is the bottleneck in the development of new drugs to reach the brain. Due to the BBB, toxic substances cannot enter the brain, but promising drug candidates also pass the BBB poorly. Suitable in vitro BBB models ar...
The goal of the present research was to present a predictivity statistical approach applied on structure-based prediction models. The approach was applied to the domain of blood-brain barrier (BBB) permeation of diverse drug-like compounds. For this...
The ability to permeate accross the blood brain barrier (BBB) is essential for drugs acting on the central nervous system (CNS). Thus, systems that allow rapid and inexpensive screening of the BBB-permeability properties of novel lead compounds are o...
Significant advancements in the field of preclinical in vitro blood-brain barrier (BBB) models have been achieved in recent years, by developing monolayer-based culture systems towards complex multi-cellular assays. The coupling of those models with...
18 October 2022
Daily exposure to xenobiotics affects human health, especially the nervous system, causing neurodegenerative diseases. The nervous system is protected by tight junctions present at the blood–brain barrier (BBB), but only molecules with desirabl...
Successful drug administration to the central nervous system requires accurate adjustment of the drugs’ molecular properties. Therefore, structure-derived descriptors of potential brain therapeutic agents are essential for an early evaluation o...
Despite its beneficial pharmacological effects in the brain, partly by modulating inositol phosphate multikinase (IPMK) activity, the therapeutic use of quercetin is limited due to its poor solubility, low oral bioavailability, and low permeability t...
Background/Objectives: Polysorbate 80 (PS80), a complex surfactant mixture, is widely recognized for its ability to enhance drug permeation across the blood–brain barrier (BBB). While this effect is generally attributed to the combined actions...
Novel stroke therapies are needed. Inhibition of the interaction between the postsynaptic density-95 (PSD-95)/disc large/ZO-1 (PDZ) domains of PSD-95 and the N-methyl-D-aspartate (NMDA) receptor has been suggested as a strategy for relieving neuronal...
Background/Objectives: The permeation behavior of new drug candidates for central nervous system (CNS) diseases is a major bottleneck in drug development. Thus, using a meaningful in vitro blood–brain barrier (BBB) model in the preclinical phas...
The log BB parameter is the logarithm of the ratio of a compound’s equilibrium concentrations in the brain tissue versus the blood plasma. This parameter is a useful descriptor in assessing the ability of a compound to permeate the blood-brain barrie...
Background: The blood brain barrier (BBB) is a dynamic and functional structure which poses a vast challenge in the development of drugs acting on the central nervous system (CNS). While most substances are denied BBB crossing, selective penetration...
Peptide oral administration is a hard goal to reach, especially if the brain is the target site. The purpose of the present study was to set up a vehicle apt to promote oral absorption of the neuropeptide dalargin (DAL), allowing it to cross the inte...
Although we have recently reported the involvement of neonatal Fc receptor (FcRn) in intranasal transport, the transport mechanisms are far from being elucidated. Ex vivo porcine olfactory tissue, primary cells from porcine olfactory epithelium (OEPC...
As the number of central nervous system (CNS) drug candidates is constantly growing, there is a strong need for precise a priori prediction of whether an administered compound is able to cross the blood–brain barrier (BBB). The aim of this stud...
The quantitative structure–activity relationship (QSAR) methodology was used to predict the blood–brain permeability (log BB) for 65 synthetic heterocyclic compounds tested as promising drug candidates. The compounds were characterized by...
Blood–brain barrier (BBB) permeability is an essential phenomena when considering the treatment of neurological disorders as well as in the case of central nervous system (CNS) adverse effects caused by peripherally acting drugs. The presented...
The acetylcholinesterase-inhibitory potential of the oleanane-type triterpenes and their glycosides from thebark of Terminalia arjuna (Combreatceae), i.e.,arjunic acid, arjunolic acid, arjungenin, arjunglucoside I, sericic acid and arjunetin, is pres...
Euphjatrophanes H–L (1–5), four new jatrophane-type and one new lathyrane-type diterpenoid, were isolated from Euphorbia peplus, along with eight known diterpenoids (6–13). Their structures were established on the basis of extensive...
The blood-brain barrier is a physical and physiological barrier that protects the brain from toxic substances within the bloodstream and helps maintain brain homeostasis. It also represents the main obstacle in the treatment of many diseases of the c...
Glioblastoma (GBM) is the most typical and aggressive form of primary brain tumor in adults, with a poor prognosis. Successful glioma treatment is hampered by ineffective medication distribution across the blood-brain barrier (BBB) and the emergence...
The permeation of the blood-brain barrier is a very important consideration for new drug candidate molecules. In this research, the reversed-phase liquid chromatography with different columns (Purosphere RP-18e, IAM.PC.DD2 and Cosmosil Cholester) was...
The migration of substances between blood circulation and central nervous system (CNS) is regulated by the blood-brain barrier (BBB). Small lipophilic molecules such as carbon dioxide, oxygen or ethanol can pass the BBB by passive, transcellular diff...
An ever-growing number of preclinical studies have investigated the tumoricidal activity of the milk thistle flavonolignan silibinin. The clinical value of silibinin as a bona fide anti-cancer therapy, however, remains uncertain with respect to its b...
Despite recent advances in tumor imaging and chemoradiotherapy, the median overall survival of patients diagnosed with glioblastoma multiforme does not exceed 15 months. Infiltration of glioma cells into the brain parenchyma, and the blood-brain bar...
Cerebral ischemia represents a particular condition among neurological diseases due to its high frequency, high associated mortality, and the permanent disability in patients that survive it. Numerous studies in animal models have demonstrated the pr...
The intranasal route of drug administration offers an opportunity to bypass the blood–brain barrier and deliver compounds directly into the brain. Scientific evidence exists for medicinal plants (e.g., Centella asiatica and Mesembryanthemum tor...
Brain tumors, especially glioblastoma, remain the most aggressive form of all the cancers because of inefficient diagnosis and profiling. Nanostructures, such as metallic nanostructures, silica nano-vehicles, quantum dots, lipid nanoparticles (NPs) a...
The field of neuronanomedicine has recently emerged as the bridge between neurological sciences and nanotechnology. The possibilities of this novel perspective are promising for the diagnosis and treatment strategies of severe central nervous system...
Central nervous system (CNS) drug disposition is dictated by a drug’s physicochemical properties and its ability to permeate physiological barriers. The blood–brain barrier (BBB), blood-cerebrospinal fluid barrier and centrally located drug transpor...
Background: Glioblastoma (GBM) remains a significant challenge in oncology due to its resistance to standard treatments including temozolomide. This study aimed to develop and validate an integrated model for predicting GBM sensitivity to alternative...
Efforts in discovering new and effective neurotherapeutics are made daily, although most fail to reach clinical trials. The main reason is their poor bioavailability, related to poor aqueous solubility, limited permeability through biological membran...
The objective of the present investigation was to study the ability of sulfobutylether-β-cyclodextrin (SBEβCD) to form an inclusion complex with sevoflurane (SEV), a volatile anesthetic with poor water solubility. The inclusion complex was prepared,...
Trans-ferulic acid (FA) is a derivative of 4-hydroxycinnamic acid, which is found in many food products, fruits and beverages. It has scientifically proven antioxidant, anti-inflammatory and antibacterial properties. However, its low ability to perme...
AD is a chronic neurodegenerative disease. Many different signaling pathways, such as Wnt/β-catenin, Notch, ROS/JNK, and PI3K/Akt/mTOR are involved in Alzheimer’s disease and crosstalk between themselves. A promising treatment involves the uses of fl...
Background/Objectives: GL-II-73 is a positive allosteric modulator that is selective for α5GABAA receptors and has physicochemical properties that favor nanocarrier formulations when parenteral delivery to the central nervous system is desired....
Lichens are a source of secondary metabolites with significant pharmacological potential. Data regarding their possible application in glioblastoma (GBM) treatment are, however, scarce. The study aimed at analyzing the mechanism of action of six lich...
Neurodegenerative disorders (NDs) affect a great number of people worldwide and also have a significant socio-economic impact on the aging population. In this context, nanomedicine applied to neurological disorders provides several biotechnological s...
The anatomical structure of the brain at the blood–brain barrier (BBB) creates a limitation for the movement of drugs into the central nervous system (CNS). Drug delivery facilitated by magneto-electric nanoparticles (MENs) is a relatively new non-in...
Predicting blood-brain barrier (BBB) permeability is essential to drug development, as a molecule cannot exhibit pharmacological activity within the brain parenchyma without first transiting this barrier. Understanding the process of permeation, howe...
In recent decades, nose-to-brain drug delivery has shown effectiveness in treating many central nervous system diseases. Intranasally administered drugs can be delivered to the brain through the olfactory and trigeminal pathways that bypass the blood...
Alzheimer’s disease is characterized by a progressive deterioration of neurons resulting in a steady loss of cognitive functions and memory. Many treatments encounter the challenge of overcoming the blood–brain barrier, thus the intranasa...
Selective butyrylcholinesterase inhibitors are considered promising drug candidates for the treatment of Alzheimer’s disease. In this work, one rivastigmine–bambuterol hybrid (MTR-1) and fourteen of its analogues were synthesized, purifie...
Human neuroscience has made remarkable progress in understanding basic aspects of functional organization; it is a renowned fact that the blood–brain barrier (BBB) impedes the permeation and access of most drugs to central nervous system (CNS)...
The blood–brain barrier (BBB) is an obstacle to the permeation of most therapeutic drugs into the brain, limiting treatments for neurological disorders. Drugs loaded within nanocarriers that pass through the BBB can overcome this limitation. Ha...
Nose-to-brain drug delivery has recently attracted enormous attention as an alternative to other delivery routes, including the most popular oral one. Due to the unique anatomical features of the nasal cavity, drugs administered intranasally can be d...
Cancer is designated as one of the principal causes of mortality universally. Among different types of cancer, brain cancer remains the most challenging one due to its aggressiveness, the ineffective permeation ability of drugs through the blood&ndas...
Common pathophysiological mechanisms have emerged for different neurological and neuropsychiatric conditions. In particular, mechanisms of oxidative stress, immuno-inflammation, and altered metabolic pathways converge and cause neuronal and non-neuro...
In the search for fused heterocycle molecules with potential biological activities, the new title compound was produced in racemic form via a four step-synthetic sequence with an overall yield of 60%. It was structurally characterised via 1H-, 13C-NM...
Microcirculation homeostasis depends on several channels permeable to ions and/or small molecules that facilitate the regulation of the vasomotor tone, hyperpermeability, the blood–brain barrier, and the neurovascular coupling function. Connexi...
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