scholarly journals Pulmonary and intranasal delivery of thymoquinone-loaded nanoparticles for Mucormycosis & Covid-19

2021 ◽  
Author(s):  
Andrei Sommer ◽  
Kurt Naber ◽  
Horst-Dieter Försterling ◽  
Ramasamy Pitchappan
Keyword(s):  
Intranasal Delivery

scholarly journals Intranasal delivery of mitochondria for treatment of Parkinson’s Disease model rats lesioned with 6-hydroxydopamine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jui-Chih Chang ◽  
Yi-Chun Chao ◽  
Huei-Shin Chang ◽  
Yu-Ling Wu ◽  
Hui-Ju Chang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Olfactory Bulb ◽  
Disease Model ◽  
Intranasal Delivery ◽  
The Difference ◽  
And Migration ◽  
6 Hydroxydopamine ◽  
Locomotor Behaviors ◽  
Migratory Stream

AbstractThe feasibility of delivering mitochondria intranasally so as to bypass the blood–brain barrier in treating Parkinson's disease (PD), was evaluated in unilaterally 6-OHDA-lesioned rats. Intranasal infusion of allogeneic mitochondria conjugated with Pep-1 (P-Mito) or unconjugated (Mito) was performed once a week on the ipsilateral sides of lesioned brains for three months. A significant improvement of rotational and locomotor behaviors in PD rats was observed in both mitochondrial groups, compared to sham or Pep-1-only groups. Dopaminergic (DA) neuron survival and recovery > 60% occurred in lesions of the substantia nigra (SN) and striatum in Mito and P-Mito rats. The treatment effect was stronger in the P-Mito group than the Mito group, but the difference was insignificant. This recovery was associated with restoration of mitochondrial function and attenuation of oxidative damage in lesioned SN. Notably, P-Mito suppressed plasma levels of inflammatory cytokines. Mitochondria penetrated the accessory olfactory bulb and doublecortin-positive neurons of the rostral migratory stream (RMS) on the ipsilateral sides of lesions and were expressed in striatal, but not SN DA neurons, of both cerebral hemispheres, evidently via commissural fibers. This study shows promise for intranasal delivery of mitochondria, confirming mitochondrial internalization and migration via RMS neurons in the olfactory bulb for PD therapy.

scholarly journals Intranasal delivery of experimental compounds in orthotopic brain tumor mouse models

2021 ◽  
Vol 2 (1) ◽  
pp. 100290
Author(s):  
Katharina M. Eyme ◽  
Litia Carvalho ◽  
Christian E. Badr
Keyword(s):  
Brain Tumor ◽  
Mouse Models ◽  
Intranasal 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.

scholarly journals The fibrin-derived γ377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease

2007 ◽  
Vol 204 (3) ◽  
pp. 571-582 ◽  
Author(s):  
Ryan A. Adams ◽  
Jan Bauer ◽  
Matthew J. Flick ◽  
Shoana L. Sikorski ◽  
Tal Nuriel ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Microglia Activation ◽  
Intranasal Delivery ◽  
Integrin Receptor ◽  
Inhibitory Peptide ◽  
Autoimmune Encephalomyelitis ◽  
Coagulation Function ◽  
Blood Brain Barrier Disruption ◽  
Brain Barrier Disruption ◽  
Experimental Autoimmune

Perivascular microglia activation is a hallmark of inflammatory demyelination in multiple sclerosis (MS), but the mechanisms underlying microglia activation and specific strategies to attenuate their activation remain elusive. Here, we identify fibrinogen as a novel regulator of microglia activation and show that targeting of the interaction of fibrinogen with the microglia integrin receptor Mac-1 (αMβ2, CD11b/CD18) is sufficient to suppress experimental autoimmune encephalomyelitis in mice that retain full coagulation function. We show that fibrinogen, which is deposited perivascularly in MS plaques, signals through Mac-1 and induces the differentiation of microglia to phagocytes via activation of Akt and Rho. Genetic disruption of fibrinogen–Mac-1 interaction in fibrinogen-γ390-396A knock-in mice or pharmacologically impeding fibrinogen–Mac-1 interaction through intranasal delivery of a fibrinogen-derived inhibitory peptide (γ377-395) attenuates microglia activation and suppresses relapsing paralysis. Because blocking fibrinogen–Mac-1 interactions affects the proinflammatory but not the procoagulant properties of fibrinogen, targeting the γ377-395 fibrinogen epitope could represent a potential therapeutic strategy for MS and other neuroinflammatory diseases associated with blood-brain barrier disruption and microglia activation.

scholarly journals Immunogenicity of a West Nile Virus DIII-Cholera Toxin A2/B Chimera after Intranasal Delivery

Toxins ◽  
2014 ◽  
Vol 6 (4) ◽  
pp. 1397-1418 ◽  
Author(s):  
Juliette Tinker ◽  
Jie Yan ◽  
Reece Knippel ◽  
Panos Panayiotou ◽  
Kenneth Cornell
Keyword(s):  
West Nile Virus ◽  
Cholera Toxin ◽  
Intranasal Delivery ◽  
West Nile

scholarly journals Pharmacokinetics, pharmacodynamics, and safety of USL261, a midazolam formulation optimized for intranasal delivery, in a randomized study with healthy volunteers

Epilepsia ◽  
2015 ◽  
Vol 56 (11) ◽  
pp. 1723-1731 ◽  
Author(s):  
Lindy L. Bancke ◽  
Heather A. Dworak ◽  
Keith A. Rodvold ◽  
Mark B. Halvorsen ◽  
Barry E. Gidal
Keyword(s):  
Healthy Volunteers ◽  
Randomized Study ◽  
Intranasal Delivery

A Microfluidics-Based Scalable Approach to Generate Extracellular Vesicles with Enhanced Therapeutic MicroRNA Loading for Intranasal Delivery to Mouse Glioblastomas

ACS Nano ◽  
2021 ◽  
Author(s):  
Kai Wang ◽  
Uday S. Kumar ◽  
Negar Sadeghipour ◽  
Tarik F. Massoud ◽  
Ramasamy Paulmurugan
Keyword(s):  
Extracellular Vesicles ◽  
Intranasal Delivery
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