Intranasal delivery of a Fas-blocking peptide attenuates Fas-mediated apoptosis in brain ischemia

Ullah, Irfan; Chung, Ki-Seok; Oh, Jungju; Beloor, Jagadish; Bae, Sumin; Lee, Sangah Clara; Lee, Minhyung; Kumar, Priti; Lee, Sangkyung

doi:10.1038/s41598-018-33296-z

Cited by 25 publications

(33 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High vascular mucous membranes of the nose facilitate rapid absorption of un-metabolized drug to the central nervous system. 7,8 Recently, novel studies have been carried out to enhance the bioavailability, such as solid dispersion, 9 liposomes, 10 chitosan microparticles, 11 polymeric lipid-core nanocapsules, 12 and lipid vesicles. 13,15 Lipid vesicles, as a tool for drug delivery of SUT, have been studied.…”

Section: Introductionmentioning

confidence: 99%

<p>Development and Evaluation of in-situ Nasal Gel Formulations of Nanosized Transferosomal Sumatriptan: Design, Optimization, in vitro and in vivo Evaluation</p>

Omar

Eleraky

Sisi

et al. 2019

DDDT

View full text Add to dashboard Cite

Background: Sumatriptan succinate (SUT) is a potent drug used for relieving or ending migraine and cluster headaches. SUT bioavailability is low (15%) when it is taken orally owing to its gastric breakdown and bloodstream before reaching the target arteries. Aim: The aim of the study was to enhance SUT bioavailability through developing an intranasal transferosomal mucoadhesive gel. Methods: SUT-loaded nanotransferosomes were prepared by thin film hydration method and characterized for various parameters such as vesicle diameter, percent entrapment efficiency (%EE), in vitro release and ex vivo permeation studies. The in-situ gels were prepared using various ratios of poloxamer 407, poloxamer 188, and carrageenan and characterized for gelation temperature, mucoadhesive strength, and rheological properties. Results: The prepared transferosomes exhibited percent entrapment efficiencies (%EE) of 40.41±3.02 to 77.47±2.85%, mean diameters of 97.25 to 245.01 nm, sustained drug release over 6 hours, and acceptable ex vivo permeation findings. The optimum formulae were incorporated into poloxamer 407 and poloxamer 188-based thermosensitive in-situ gel using carrageenan as a mucoadhesive polymer. Pharmacokinetic evaluation showed that the prepared in-situ gel of SUT-loaded nano-transferosomes gave enhanced bioavailability, 4.09fold, as compared to oral drug solution. Conclusion: Based on enhancing the bioavailability and sustaining the drug release, it can be concluded that the in-situ gel of SUT-loaded nano-transferosomes were developed as a promising non-invasive drug delivery system for treating migraine.

show abstract

Section: Introductionmentioning

confidence: 99%

<p>Development and Evaluation of in-situ Nasal Gel Formulations of Nanosized Transferosomal Sumatriptan: Design, Optimization, in vitro and in vivo Evaluation</p>

Omar

Eleraky

Sisi

et al. 2019

DDDT

View full text Add to dashboard Cite

show abstract

“…There are other apparent advantages of intranasal administration including: convenience of administration, a possibility for repeated administration, minimal delivery time, no need for applying cytokine modification strategies to penetrate blood-brain barrier, absence of systemic side effects [20][21][22]. In agreement with this notion, clinical effects of cytokines after intranasal administration have been demonstrated in various models of neuropathology, including Alzheimer disease, brain ischemia, and traumatic brain injury [23,24,33,34].…”

Section: Discussionmentioning

confidence: 97%

Intranasal delivery of M2 macrophage-derived soluble products reduces neuropsychological deficit in patients with cerebrovascular disease: a pilot study

Shevela

Davydova

Старостина

et al. 2019

Journal of Neurorestoratology

View full text Add to dashboard Cite

Objective:We assessed the safety and clinical effectiveness of intranasal therapy with M2 macrophage-derived soluble products (M2-SPs) for treating patients with cerebrovascular disease (CVD).Materials and methods:The protocol of the study was registered at www.ClinicalTrails.gov (NCT02957123). The study group comprised 30 patients with chronic CVD. Neurological status was examined before therapy and at 1- and 6-month follow–up. Concentrations of 32 cytokines in the blood serum were evaluated before and 1 month after therapy onset. Neurological assessment was conducted with the following scales: Subjective Assessment of Clinical (neurological) Symptoms (SACS), Hospital Anxiety and Depression Scale (HADS), Functional Mobility Assessment in Eldery Patients (FMA), and Montreal Cognitive Assessment (MoCa).Results:M2-SPs treatment (once daily for 28~30 days) was found to be safe and well tolerated. Neuropsychological improvements showed the amelioration of neurological symptoms, reduction in anxiety and depression levels, improvement in balance and gait ability as well as cognitive functions. Clinical effects could be detected at the end of treatment course and was stable during 6-month follow-up. Blood serum cytokine evaluation demonstrated diminished baseline levels of many cytokines including those with neurotrophic activity (brain-derived neurotrophic factor, BDNF; hepatocyte growth factor, HGF; migration inhibitory factor, MIF). Upon treatment, most pronounced clinical responses were observed in patients with most severe cytokine deficiency and post-therapy normalization of MIF and HGF levels.Conclusion:Intranasal therapy with M2-SPs is safe and according to preliminary data reduces neuropsychological deficit in patients with chronic CVD. The positive effect of M2-SPs treatment seems to be HGF- and MIF-dependent.

show abstract

“…Recently, very early treatment with zonisamide was shown to decrease morbidity by suppressing the expression of caspase-3, caspase-8, and calpain-1, inhibiting the apoptosis of neuronal cells after cerebral ischemia ( He et al, 2021 ). Further, intranasal administration of a Fas-blocking peptide 12 h after ischemic stroke attenuated Fas-mediated apoptosis, decreased the volume of the infarcted area, and reduced neurological deficits ( Ullah et al, 2018 ). Importantly, a significant reduction in the volume of the infarcted area occurred in hybrid mice expressing nonfunctional Fas ligand and in TNF knockout mice 24 h after stroke ( Martin-Villalba et al, 1999 ; Rosenbaum et al, 2000 ).…”

Section: Discussionmentioning

confidence: 99%

Very early environmental enrichment protects against apoptosis and improves functional recovery from hypoxic–ischemic brain injury

Lee

Song

Hwang

et al. 2023

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Appropriate rehabilitation of stroke patients at a very early phase results in favorable outcomes. However, the optimal strategy for very early rehabilitation is at present unclear due to the limited knowledge on the effects of very early initiation of rehabilitation based on voluntary exercise (VE). Environmental enrichment (EE) is a therapeutic paradigm for laboratory animals that involves complex combinations of physical, cognitive, and social stimuli, as well as VE. Few studies delineated the effect of EE on apoptosis in very early stroke in an experimental model. Although a minimal benefit of early rehabilitation in stroke models has been claimed in previous studies, these were based on a forced exercise paradigm. The aim of this study is to determine whether very early exposure to EE can effectively regulate Fas/FasL-mediated apoptosis following hypoxic–ischemic (HI) brain injury and improve neurobehavioral function. C57Bl/6 mice were housed for 2 weeks in either cages with EE or standard cages (SC) 3 h or 72 h after HI brain injury. Very early exposure to EE was associated with greater improvement in motor function and cognitive ability, reduced volume of the infarcted area, decreased mitochondria-mediated apoptosis, and decreased oxidative stress. Very early exposure to EE significantly downregulated Fas/FasL-mediated apoptosis, decreased expression of Fas, Fas-associated death domain, cleaved caspase-8/caspase-8, cleaved caspase-3/caspase-3, as well as Bax and Bcl-2, in the cerebral cortex and the hippocampus. Delayed exposure to EE, on the other hand, failed to inhibit the extrinsic pathway of apoptosis. This study demonstrates that very early exposure to EE is a potentially useful therapeutic translation for stroke rehabilitation through effective inhibition of the extrinsic and intrinsic apoptotic pathways.

show abstract

Intranasal delivery of a Fas-blocking peptide attenuates Fas-mediated apoptosis in brain ischemia

Cited by 25 publications

References 65 publications

<p>Development and Evaluation of in-situ Nasal Gel Formulations of Nanosized Transferosomal Sumatriptan: Design, Optimization, in vitro and in vivo Evaluation</p>

<p>Development and Evaluation of in-situ Nasal Gel Formulations of Nanosized Transferosomal Sumatriptan: Design, Optimization, in vitro and in vivo Evaluation</p>

Intranasal delivery of M2 macrophage-derived soluble products reduces neuropsychological deficit in patients with cerebrovascular disease: a pilot study

Very early environmental enrichment protects against apoptosis and improves functional recovery from hypoxic–ischemic brain injury

Contact Info

Product

Resources

About