This review describes specific strategies for targeting to the central nervous system (CNS). Systemically administered drugs can reach the brain by crossing one of two physiological barriers resistant to free diffusion of most molecules from blood to CNS: the endothelial blood-brain barrier or the epithelial blood-cerebrospinal fluid barrier. These tissues constitute both transport and enzymatic barriers. The most common strategy for designing effective prodrugs relies on the increase of parent drug lipophilicity. However, increasing lipophilicity without a concomitant increase in rate and selectivity of prodrug bioconversion in the brain will result in failure. In these regards, consideration of the enzymes present in brain tissue and in the barriers is essential for a successful approach. Nasal administration of lipophilic prodrugs can be a promising alternative non-invasive route to improve brain targeting of the parent drugs due to fast absorption and rapid onset of drug action. The carrier-mediated absorption of drugs and prodrugs across epithelial and endothelial barriers is emerging as another novel trend in biotherapeutics. Several specific transporters have been identified in boundary tissues between blood and CNS comp...Continue Reading
Transport of steroid hormones through the rat blood-brain barrier. Primary role of albumin-bound hormone
Inhibition of GABA uptake in rat brain slices by nipecotic acid, various isoxazoles and related compounds
"Mixed inhibitor-prodrug" as a new approach toward systemically active inhibitors of enkephalin-degrading enzymes
Simultaneous delivery of valproic acid and glycine to the brain. Deamination of 2-propylpentylglycinamide by monoamine oxidase B
The gamma-hydroxybutyrate model of absence seizures: correlation of regional brain levels of gamma-hydroxybutyric acid and gamma-butyrolactone with spike wave discharges
Pharmacokinetics of chlorambucil-tertiary butyl ester, a lipophilic chlorambucil derivative that achieves and maintains high concentrations in brain
Immunohistochemical localization of aminopeptidase M in rat brain and periphery: relationship of enzyme localization and enkephalin metabolism
Blood-brain barrier: penetration of morphine, codeine, heroin, and methadone after carotid injection
Dosage form design for improvement of bioavailability of levodopa III: Influence of dose on pharmacokinetic behavior of levodopa in dogs and Parkinsonian patients
Synthesis and pharmacological properties of 2-[S-acetylthiorphan]-1,3- diacylaminopropan-2-ol derivatives as chimeric lipid drug carriers containing an enkephalinase inhibitor
Synthesis and evaluation of a redox chemical delivery system for brain-enhanced dopamine containing an activated carbamate-type ester
Glycopeptide enkephalin analogues produce analgesia in mice: evidence for penetration of the blood-brain barrier
Enhanced brain delivery of an anti-HIV nucleoside 2'-F-ara-ddI by xanthine oxidase mediated biotransformation
Determination of m-nitrophenol and nipecotic acid in mouse tissues by high-performance liquid chromatography after administration of the anticonvulsant m-nitrophenyl-3-piperidinecarboxylate hydrochloride
Antiepileptic drug pharmacokinetics and neuropharmacokinetics in individual rats by repetitive withdrawal of blood and cerebrospinal fluid: milacemide
Proton transport across transient single-file water pores in a lipid membrane studied by molecular dynamics simulations
Glucose transport in immortalized rat brain capillary endothelial cells in vitro: transport activity and GLUT1 expression
Role of brain tissue localized purine metabolizing enzymes in the central nervous system delivery of anti-HIV agents 2'-beta-fluoro-2',3'-dideoxyinosine and 2'-beta-fluoro-2',3'-dideoxyadenosine in rats
Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98).
Identification of a membrane protein, LAT-2, that Co-expresses with 4F2 heavy chain, an L-type amino acid transport activity with broad specificity for small and large zwitterionic amino acids.
Identification and functional characterization of a Na+-independent neutral amino acid transporter with broad substrate selectivity.
Human placental sodium-dependent vitamin C transporter (SVCT2): molecular cloning and transport function
Cloning and functional characterization of the human sodium-dependent vitamin C transporters hSVCT1 and hSVCT2
Systemically administered D-glucose conjugates of 7-chlorokynurenic acid are centrally available and exert anticonvulsant activity in rodents
Substrate-based fragment identification for the development of selective, nonpeptidic inhibitors of striatal-enriched protein tyrosine phosphatase
Large amino acid transporter 1 (LAT1) prodrugs of valproic acid: new prodrug design ideas for central nervous system delivery
Prodrugs of nonsteroidal anti-inflammatory drugs (NSAIDs), more than meets the eye: a critical review
Drug targeting to brain: a systematic approach to study the factors, parameters and approaches for prediction of permeability of drugs across BBB
Influence of chitosan glutamate on the in vivo intranasal absorption of rokitamycin from microspheres
Glucose Transporters at the Blood-Brain Barrier: Function, Regulation and Gateways for Drug Delivery
The promiscuous binding of pharmaceutical drugs and their transporter-mediated uptake into cells: what we (need to) know and how we can do so
Pharmaceutical drug transport: the issues and the implications that it is essentially carrier-mediated only.
Lipid nanoparticles with different oil/fatty ester ratios as carriers of buprenorphine and its prodrugs for injection
Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer
Medicinal chemistry based approaches and nanotechnology-based systems to improve CNS drug targeting and delivery
Development of Fluorine-18 Labeled Metabolically Activated Tracers for Imaging of Drug Efflux Transporters with Positron Emission Tomography
Nanoparticles of 2-deoxy-D-glucose functionalized poly(ethylene glycol)-co-poly(trimethylene carbonate) for dual-targeted drug delivery in glioma treatment
Multidrug resistance in cancer or inefficacy of neuroactive agents: innovative strategies to inhibit or circumvent the active efflux transporters selectively
Chemical Approach to Positional Isomers of Glucose-Platinum Conjugates Reveals Specific Cancer Targeting through Glucose-Transporter-Mediated Uptake in Vitro and in Vivo
Carbohydrate-Neuroactive Hybrid Strategy for Metabolic Glycan Engineering of the Central Nervous System in Vivo
Therapeutic strategies and nano-drug delivery applications in management of ageing Alzheimer's disease
Chirality of Central Nervous System (CNS) Acting Drugs: A Formidable Therapeutic Hurdle Against CNS Diseases
Amphetamine decorated cationic lipid nanoparticles cross the blood-brain barrier: therapeutic promise for combating glioblastoma.
Design and exploratory neuropharmacological evaluation of novel thyrotropin-releasing hormone analogs and their brain-targeting bioprecursor prodrugs
Hyperpolarization of 15 N-pyridinium and 15 N-aniline derivatives by using parahydrogen: new opportunities to store nuclear spin polarization in aqueous media
Combined strategies of apomorphine diester prodrugs and nanostructured lipid carriers for efficient brain targeting
Cell-Penetrating Peptides: As a Promising Theranostics Strategy to Circumvent the Blood-Brain Barrier for CNS Diseases.
Blood Brain Barrier Regulation in Health & Disease
The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.
Blood Brain Barrier
The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.
Blood Brain Barrier Chips
The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.
Blood-Brain Barrier Transport in Neurodegeneration
The blood brain barrier is important for regulating the movement of biomolecules in and out of the brain. For example, membrane transporters in the blood brain barrier can be essential for regulating drug movement and dysregulation of these processes may play a role in neurodegeneration. This feed follows the latest research on this topic.