Release rate is a key variable affecting the therapeutic effectiveness of liposomal fasudil for the treatment of cerebral ischemia/reperfusion injury

Yanagida, Yosuke; Namba, Mio; Fukuta, Tatsuya; Yamamoto, Hisako; Yanagida, Mitsuaki; Honda, Miki; Oku, Naoto; Asai, Tomohiro

doi:10.1016/j.bbrc.2020.07.038

Cited by 6 publications

(6 citation statements)

References 23 publications

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“…Yanagida et al reported the impact of the rate of drug release on cerebroprotective effects in cerebral I/R injury using four formulations of Fasudil-Lip by changing the main lipid compositions (distearoylphosphatidylcholine or dipalmitoylphosphatidylcholine) and internal water phases (ammonium citrate or ammonium sulfate). The authors found the therapeutic effects of Fasudil-Lip with a slow drug release rate to be much lower than that with a moderately fast one and suggested that optimization of drug-release properties is likely important to augment the therapeutic outcome of liposomal neuroprotective agents for treating cerebral I/R injury [28].…”

Section: Delivery Of Neuroprotective Agents Using Liposomesmentioning

confidence: 99%

“…Asialo-erythropoietin (AEPO) Anti-apoptotic effect through binding to EPO receptors Reduced damaged brain volume via anti-apoptosis and improved motor functional deficits [22,24] Fasudil Inhibition of Rho-kinase activation Suppressed neutrophil infiltration and ameliorated ischemic brain damage [25,28] FK506 (Tacrolimus) Anti-inflammatory effect via calcineurin inhibition Ameliorated ischemic brain damage by anti-inflammatory and anti-apoptotic effects from acute to subacute phases [31,32] Cyclosporin A Anti-inflammatory effect via calcineurin inhibition Suppressed inflammation through inhibition of release of inflammatory cytokines from immune cells and neurons [34] ZL006 To identify a novel targeting peptide for the region of ischemic stroke, Hong et al performed an in vivo phage display using t-MCAO rats [47]. Through three cycles of in vivo screening, the authors identified a candidate peptide, namely CLEVSRKNC, termed strokehoming peptide (SHp).…”

Section: Drug Main Mechanism Of Action Effectiveness Referencesmentioning

confidence: 99%

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Application and Utility of Liposomal Neuroprotective Agents and Biomimetic Nanoparticles for the Treatment of Ischemic Stroke

2022

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Ischemic stroke is still one of the leading causes of high mortality and severe disability worldwide. Therapeutic options for ischemic stroke and subsequent cerebral ischemia/reperfusion injury remain limited due to challenges associated with drug permeability through the blood-brain barrier (BBB). Neuroprotectant delivery with nanoparticles, including liposomes, offers a promising solution to address this problem, as BBB disruption following ischemic stroke allows nanoparticles to pass through the intercellular gaps between endothelial cells. To ameliorate ischemic brain damage, a number of nanotherapeutics encapsulating neuroprotective agents, as well as surface-modified nanoparticles with specific ligands targeting the injured brain regions, have been developed. Combination therapy with nanoparticles encapsulating neuroprotectants and tissue plasminogen activator (t-PA), a globally approved thrombolytic agent, has been demonstrated to extend the narrow therapeutic time window of t-PA. In addition, the design of biomimetic drug delivery systems (DDS) employing circulating cells (e.g., leukocytes, platelets) with unique properties has recently been investigated to overcome the injured BBB, utilizing these cells’ inherent capability to penetrate the ischemic brain. Herein, we review recent findings on the application and utility of nanoparticle DDS, particularly liposomes, and various approaches to developing biomimetic DDS functionalized with cellular membranes/membrane proteins for the treatment of ischemic stroke.

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Section: Delivery Of Neuroprotective Agents Using Liposomesmentioning

confidence: 99%

Section: Drug Main Mechanism Of Action Effectiveness Referencesmentioning

confidence: 99%

Application and Utility of Liposomal Neuroprotective Agents and Biomimetic Nanoparticles for the Treatment of Ischemic Stroke

2022

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“…The role played by drug lipid ratio was found to be of great significance in the case of liposomal vincristine formulations in controlling the drug release rate and antitumour efficacy [34] . In a pharmacokinetics study for the treatment of cerebral ischemia/reperfusion injury, release properties of fasudil were found to vary with lipid composition and internal phase of the liposomes [35] . In fact, the maximum therapeutic index among different formulations was observed with a mid-level release rate of fasudil from liposomes.…”

Section: Drug Releasementioning

confidence: 99%

“…However, Doxil ® [30] was the first drug approved in the United States of America (USA) in the year 1995. Since then, several drugs have completed their clinical trials and are currently in use for the treatment of cancer, tumours, fungal infections etc., and many more are in different phases of clinical trials [35,121] . Table 1 of the various drugs approved for clinical applications.…”

Section: Liposomes In Clinical Usementioning

confidence: 99%

Liposome Assisted Drug Delivery-An Updated Review

Agarwal¹

2022

IJPS

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Agarwal: Liposome Assisted Drug DeliveryAfter extensive work spanning more than half a century, liposomes have crossed the chasm and emerged as a prominent candidate in mainstream drug delivery. Post the historic launch of the first liposome-based drug, it is in the last three decades when liposome technology has slowly transformed from a research apparatus to a versatile drug carrier system influencing many biomedical areas. Liposomes have the ability to deliver a drug to a target site with the least amount of systemic toxicity by overcoming hurdles of cellular and tissue uptake, stabilizing therapeutic compounds, and improving biodistribution. They have been investigated for diverse applications such as treatment of cancer, delivery of gene and vaccine, treatment of lung and skin diseases, treatment of tumours, and imaging tumours at the site of infection. They are leading present-day smart delivery systems due to their flexible biophysical and physicochemical properties, which permit easy control to address different delivery concerns. This review will discuss various advances and updates in liposome-assisted drug delivery and the current clinical use of liposomes for biomedical applications.

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“…Fasudil, a Rho kinase inhibitor, has been extensively reported to relieve vasospasm in patients with subarachnoid hemorrhage (SAH) by inhibiting the phosphorylation of myosin light chain (MLC) [9,10]. In addition, several studies revealed that Fasudil has other effects, including anti-in ammatory, antiapoptosis, reducing oxidative stress and ischemia-reperfusion [11,12].Fasudil also exert neuroprotective effect and attenuate cognitive function in some neurodegenerative diseases [13]. For example, Kumar et.…”

Section: Introductionmentioning

confidence: 99%

Fasudil attenuates Neuro-Inflammation and Oxidative Stress via Rhoa/Rock Pathways in Delayed Neuropsychologic Sequelae Mice Model

Yan

Fang

Gao

et al. 2021

Preprint

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Background Delayed neuropsychologic sequelae is common in patients after carbon monoxide poisoning without effective methods worldwide. Fasudil exerts neuroprotective effect and alleviates oxidative stress in some neurodegenerative disorders. However, the mechanism between DNS and FS remains unclear. The study aims to explore the efficacy and mechanism of Fasudil in DNS mice model. Objective The delayed neuropsychologic sequelae model was induced with a hyperbaric oxygen chamber. All rats were randomly assigned to three groups (n=10): air control group (AC), CO poisoning group (CO), and CO poisoning +Fasudil group (CO+FS). Rats in the CO+FS group were given Fasudil (10 mg/kg/day, ip). The morris water maze was documented to estimate spatial learning and memory of mice. The demyelination state in brain was observed through LFB staining. The protein of MBP was examined with immunofluorescence staining. The levels of IL-6, TNF-α, TGF-β, SOD, and MDA were examined by ELISA. The mRNA levels of Rho, ROCK2, MLC1 and MYPT1 were analyzed by rt-PCR. Result The cognitive impairment in the CO+FS group were significantly reduced than those of the CO group (P<0.05). LFB staining and immunofluorescence staining of MBP results showed that FS significantly treatment attenuated demyelination (P<0.05). Compared with the CO group, the levels of TNF-α, IL-6, MDA, ROCK2, MLC1, and MYPT1 significantly decreased (P<0.05), and the levels of SOD were significantly increased in the CO+FS group (P<0.05). Conclusion In a word, Fasudil attenuated delayed neuropsychologic sequelae by inhibiting inflammation, oxidative stress and downregulating Rho/ROCK pathway in DNS mice model. We conclude that Fasudil may be a novel treatment for delayed neuropsychologic sequelae.

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Release rate is a key variable affecting the therapeutic effectiveness of liposomal fasudil for the treatment of cerebral ischemia/reperfusion injury

Cited by 6 publications

References 23 publications

Application and Utility of Liposomal Neuroprotective Agents and Biomimetic Nanoparticles for the Treatment of Ischemic Stroke

Application and Utility of Liposomal Neuroprotective Agents and Biomimetic Nanoparticles for the Treatment of Ischemic Stroke

Liposome Assisted Drug Delivery-An Updated Review

Fasudil attenuates Neuro-Inflammation and Oxidative Stress via Rhoa/Rock Pathways in Delayed Neuropsychologic Sequelae Mice Model

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