Application of CPPs for Brain Delivery

2015 ◽  
pp. 349-356 ◽  
Author(s):  
Artita Srimanee ◽  
Jakob Regberg ◽  
Ülo Langel
Keyword(s):  
Brain Delivery

Preparation and analysis of nanocarriers for brain delivery of neuroprotective andrographolide

Planta Medica ◽  
2015 ◽  
Vol 81 (16) ◽  
Author(s):  
C Guccione ◽  
V Piazzini ◽  
MC Bergonzi ◽  
M Oufir ◽  
D Eigenmann ◽  
...  
Keyword(s):  
Brain Delivery

Neurotoxicity and Neuroprotective Effects of Polyimides (PI) and Polyphenylenevinylene (PPV) against Hydrogen Peroxide (H2O2)

2011 ◽  
Vol 8 (2) ◽  
pp. 33
Author(s):  
Norfaezah Mazalan ◽  
Mazatulikhma Mat Zain ◽  
Nor Saliyana Jumali ◽  
Norhanim Mohalid ◽  
Zurina Shaameri ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Drug Delivery Systems ◽  
Neuronal Cells ◽  
Water Soluble ◽  
Brain Delivery ◽  
Specific Therapy ◽  
Neuroprotective Effects ◽  
Water Soluble Polymer ◽  
Site Specific ◽  
Novel Drugs

Recently, research and development in the field of drug delivery systems (DDS) facilitating site-specific therapy has reached significant progression. DDS based on polymer micelles, coated micro- and nanoparticles, and various prodrug systems including water-soluble polymer have been prepared and extensively studied as novel drugs designed for cancer chemotherapy and brain delivery. Since polymers are going to be used in human, this study has the interest of testing two types of polymer, polyimides (PI) and polyphenylenevinylene (PPV) on neuronal cells. The objective of this study was to determine the possible neurotoxicity and potential neuroprotective effects of PI and PPV towards SH-SY5Y neuronal cells challenged by hydrogen peroxide (H2O2) as an oxidant. Cells were pretreated with either PI or PPV for 1 hour followed by incubation for 24 hour with 100 µM of H2O2. MTS assay was used to assess cell viability. Results show that PI and PPV are not harmful within the concentration up to 10 µM and 100 µM, respectively. However, PI and PPV do not protect neuronal cells against toxicity induced by H2O2 or further up the cell death.

scholarly journals hNGF Peptides Elicit the NGF-TrkA Signalling Pathway in Cholinergic Neurons and Retain Full Neurotrophic Activity in the DRG Assay

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 216 ◽  
Author(s):  
Viviana Triaca ◽  
Elena Fico ◽  
Valentina Sposato ◽  
Silvia Caioli ◽  
Maria Teresa Ciotti ◽  
...  
Keyword(s):  
Dorsal Root ◽  
Cholinergic Neurons ◽  
Early Gene ◽  
Low Molecular Weight ◽  
Primary Neurons ◽  
Brain Delivery ◽  
Drg Neurons ◽  
Neurotrophic Activity ◽  
Mapk Signalling

In the last decade, Nerve Growth Factor (NGF)-based clinical approaches have lacked specific and efficient Tyrosine Kinase A (TrkA) agonists for brain delivery. Nowadays, the characterization of novel small peptidomimetic is taking centre stage in preclinical studies, in order to overcome the main size-related limitation in brain delivery of NGF holoprotein for Central Nervous System (CNS) pathologies. Here we investigated the NGF mimetic properties of the human NGF 1–14 sequence (hNGF1–14) and its derivatives, by resorting to primary cholinergic and dorsal root ganglia (DRG) neurons. Briefly, we observed that: 1) hNGF1–14 peptides engage the NGF pathway through TrkA phosphorylation at tyrosine 490 (Y490), and activation of ShcC/PI3K and Plc-γ/MAPK signalling, promoting AKT-dependent survival and CREB-driven neuronal activity, as seen by levels of the immediate early gene c-Fos, of the cholinergic marker Choline Acetyltransferase (ChAT), and of Brain Derived Neurotrophic Factor (BDNF); 2) their NGF mimetic activity is lost upon selective TrkA inhibition by means of GW441756; 3) hNGF1–14 peptides are able to sustain DRG survival and differentiation in absence of NGF. Furthermore, the acetylated derivative Ac-hNGF1–14 demonstrated an optimal NGF mimetic activity in both neuronal paradigms and an electrophysiological profile similar to NGF in cholinergic neurons. Cumulatively, the findings here reported pinpoint the hNGF1–14 peptide, and in particular its acetylated derivative, as novel, specific and low molecular weight TrkA specific agonists in both CNS and PNS primary neurons.

scholarly journals Systematic development of lectin conjugated microspheres for nose-to-brain delivery of rivastigmine for the treatment of Alzheimer’s disease

2021 ◽  
Vol 141 ◽  
pp. 111829
Author(s):  
Yang Gao ◽  
Waleed H. Almalki ◽  
Obaid Afzal ◽  
Sunil K. Panda ◽  
Imran Kazmi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Delivery ◽  
Systematic Development

Clozapine loaded nanostructured lipid carriers engineered for brain targeting via nose-to-brain delivery: Optimization and in vivo pharmacokinetic studies

2021 ◽  
pp. 102533
Author(s):  
Hetal P. Patel ◽  
Priyanshi A. Gandhi ◽  
Priyanka S. Chaudhari ◽  
Bhargavi V. Desai ◽  
Ditixa T. Desai ◽  
...  
Keyword(s):  
Nanostructured Lipid Carriers ◽  
Brain Targeting ◽  
Pharmacokinetic Studies ◽  
Brain Delivery

Neuropharmacokinetic evaluation of lactoferrin-treated indinavir-loaded nanoemulsions: remarkable brain delivery enhancement

2019 ◽  
Vol 45 (5) ◽  
pp. 736-744 ◽  
Author(s):  
Zahra Karami ◽  
Mohammad Reza Saghatchi Zanjani ◽  
Saeed Rezaee ◽  
Kobra Rostamizadeh ◽  
Mehrdad Hamidi
Keyword(s):  
Brain Delivery

scholarly journals Application of the quality-by-design (QbD) approach to improve the nose-to-brain delivery of diazepam-loaded nanostructured lipid carriers (NLC)

2020 ◽  
Author(s):  
Cláudia Costa ◽  
Sara Cunha ◽  
Andreia Peixoto ◽  
João Moreira ◽  
José Sousa Lobo ◽  
...  
Keyword(s):  
Quality By Design ◽  
Nanostructured Lipid Carriers ◽  
Brain Delivery

scholarly journals Intranasal Allopregnanolone Confers Rapid Seizure Protection: Evidence for Direct Nose-to-Brain Delivery

2021 ◽  
Author(s):  
Dorota Zolkowska ◽  
Chun-Yi Wu ◽  
Michael A. Rogawski
Keyword(s):  
Adverse Effects ◽  
Screen Test ◽  
Brain Regions ◽  
Seizure Threshold ◽  
Brain Delivery ◽  
Intranasal Delivery ◽  
Behavioral Impairment ◽  
Loss Of Righting Reflex ◽  
Ptz Test ◽  
Central Nervous System Activity

AbstractAllopregnanolone, a positive modulator of GABAA receptors with antiseizure activity, has potential in the treatment of seizure emergencies. Instillation of allopregnanolone in 40% sulfobutylether-β-cyclodextrin into the nose in mice rapidly elevated the seizure threshold in the timed intravenous pentylenetetrazol (ED50, 5.6 mg/kg), picrotoxin (ED50, 5.9 mg/kg), and bicuculline seizure tests. The effect peaked at 15 min, decayed over 1 h, and was still evident in some experiments at 6 h. Intranasal allopregnanolone also delayed the onset of seizures in the maximal PTZ test. At an allopregnanolone dose (16 mg/kg) that conferred comparable effects on seizure threshold as the benzodiazepines midazolam and diazepam (both at doses of 1 mg/kg), allopregnanolone caused minimal sedation or motor toxicity in the horizontal screen test whereas both benzodiazepines produced marked behavioral impairment. In addition, intranasal allopregnanolone failed to cause loss-of-righting reflex in most animals, but when the same dose was administered intramuscularly, all animals became impaired. Intranasal allopregnanolone (10 mg/kg) caused a rapid increase in brain allopregnanolone with a Tmax of ~5 min after initiation of the intranasal delivery. High levels of allopregnanolone were recovered in the olfactory bulb (Cmax, 16,000 ng/mg) whereas much lower levels (Cmax, 670 ng/mg) were present in the remainder of the brain. We conclude that the unique ability of intranasal allopregnanolone to protect against seizures without inducing behavioral adverse effects is due in part to direct nose-to-brain delivery, with preferential transport to brain regions relevant to seizures. Benzodiazepines are commonly administered intranasally for acute seizure therapy, including for the treatment of acute repetitive seizures, but are not transported from nose-to-brain. Intranasal allopregnanolone acts with greater speed, has less propensity for adverse effects, and has the ability to overcome benzodiazepine refractoriness. This is the first study demonstrating rapid functional central nervous system activity of a nose-to-brain-delivered steroid. Intranasal delivery circumvents the poor oral bioavailability of allopregnanolone providing a route of administration permitting its evaluation as a treatment for diverse neuropsychiatric indications.

Sign in / Sign up

Export Citation Format

Share Document