Self-nanomicellizing solid dispersion of edaravone: part I &amp;ndash; oral bioavailability improvement

Parikh, Ankit; Kathawala, Krishna; Tan, Chun Chuan; Garg, Sanjay; Zhou, Xin‐Fu

doi:10.2147/dddt.s161940

Cited by 26 publications

(10 citation statements)

References 70 publications

(132 reference statements)

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“…As terpinen-4-ol is the major component of TTO, it has been used as the primary reference standard [ 2 ]. The analysis was conducted with an isocratic method using a PhenoSphere-NEXT™ 5µm C18 120 (250 × 4.6 mm) analytical column (Phenomenex, Torrance, CA, USA) at 40 °C, which is connected to an HPLC system (Shimadzu Corporation, Kyoto, Japan) consisting of a Diode Array Detector (SPD-M20A), an online degasser (DGU-20A3), a system controller (CBM-20A), an autosampler (SIL-20AHT), a pump (LC20AD), and an LC solution Chromopac data processor [ 33 , 34 ]. The mobile phase was a mixture of methanol and water (90:10, v/v ) eluted at a flow rate of 1.0 mL/min.…”

Section: Methodsmentioning

confidence: 99%

Quality-by-Design Approach for the Development of Nano-Sized Tea Tree Oil Formulation-Impregnated Biocompatible Gel with Antimicrobial Properties

et al. 2020

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Despite the promising properties of tea tree oil (TTO) as potential therapeutics for several superficial skin conditions, certain limitations such as physical instability and skin irritation have restricted its widespread use. This study focuses on developing a rationally designed lipid-based nanoformulation (TTO-LNF) in accordance with the US Food and Drug Administration standard using a well-recognized quality-by-design (QbD) approach. Using a mixture experimental design, TTO-LNF has been optimized with 5% TTO, 10% surfactant, 5% co-surfactant, and 80% water, which showed a 14.4 ± 4.4 nm droplet size and 0.03 ± 0.01 polydispersity index (PDI). To ease the topical administration, the TTO-LNF gel formulation was further developed using xanthan gum to achieve the desired viscosity and form a gel. The in vitro antibacterial tests of TTO-LNF showed promising inhibitory effects toward both Gram-negative and Gram-positive bacteria. In fact, a complete growth inhibition of S. epidermidis was observed when exposed to TTO-LNF and TTO-LNF gel for 24 h, showing better activity than antibiotic kanamycin (25 µg/mL). Additionally, the in vitro release study showed a sustained release profile with a 50% release in 24 h, which could be beneficial to reduce the toxicity and thereby improve the therapeutic efficacy for long-acting applications. Furthermore, the formulations were remarkably stable at 40 °C/75% Relative humidity (RH) for at least 4 weeks. Therefore, this study presents a promising strategy to develop a biocompatible and stable formulation that can be used for the topical treatment of skin infections.

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Section: Methodsmentioning

confidence: 99%

Quality-by-Design Approach for the Development of Nano-Sized Tea Tree Oil Formulation-Impregnated Biocompatible Gel with Antimicrobial Properties

et al. 2020

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“…To achieve our goal, we used a novel oral formulation of Edaravone that was previously designed by Parikh et al [41]. Edaravone exhibits poor oral bioavailability (5.23%) [70] that requires its administration trough intravenous route.…”

Section: Discussionmentioning

confidence: 99%

“…This model also shows signs of mitochondrial dysfunction that becomes signi cant at advanced age [40]. The novel oral formulation of Edaravone was designed earlier in our laboratory by using self-nano micellizing solid dispersion strategy and proved to be safe and effective in vitro and in AD animal model [41,34].…”

Section: Introductionmentioning

confidence: 99%

A Novel Oral Edaravone Formulation Partially Alleviates Tau Pathology and Motor Deficits in an Animal Model of Frontotemporal Dementia

Kelliny

Xiong

Bobrovskaya

et al. 2021

Preprint

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Oxidative stress (OS) is a key factor in the pathogenesis of several neurodegenerative disorders and is involved in the accumulation of amyloid beta plaques and Tau inclusions. Edaravone (EDR) is a free radical scavenger that is approved for motor neuron disease and acute ischemic stroke. EDR alleviates pathologies and cognitive impairment of AD via targeting multiple key pathways in transgenic mice. Herein, we aimed to study the effect of EDR on Tau pathology in an animal model (P301L mice) of frontotemporal dementia (FTD) at two age time points representing the early and late stages of the disease. A novel EDR formulation was utilized in the study and the drug was delivered orally in drinking water for 3 months. Then, behavioral tests were conducted followed by animal sacrifice and brain dissection. Treatment with EDR improved the cognitive deficits as evaluated in Morris water maze, novel object recognition and significantly alleviated motor deficits in these mice. EDR also reduced the levels of 4-hydroxy-2-nonenal (4-HNE) and 3-nitrotyrosine (3-NT) adducts. In addition, immunohistochemistry showed that EDR reduced tau phosphorylation and neuroinflammation and partially rescued neurons against oxidative neurotoxicity. Moreover, EDR attenuated downstream pathologies involved in Tau hyperphosphorylation. These results suggest that EDR may be a potential therapeutic agent for the treatment of FTD.

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“…Nonetheless, its progress to clinical use has been impeded by its poor oral bioavailability associated with its physiochemical properties [26]. Previously, Parikh and colleagues from our laboratory developed novel oral formulations of edaravone (EDR) and curcumin (CUR) using soluplus, a polymer as a drug carrier [27,28]. These novel formulations had improved physical properties and oral bioavailability, and were shown to have protective effects in animal models of Alzheimer's disease (AD) [29,30].…”

Section: Introductionmentioning

confidence: 99%

The Effects of Novel Formulations of Edaravone and Curcumin in the Mouse Intrastriatal Lipopolysaccharide Model of Parkinson’s Disease

Deng¹,

Garg²,

Zhou³

et al. 2022

Front. Biosci. (Schol Ed)

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The major hallmark of Parkinson's disease (PD) is the degeneration of dopaminergic neurons in the substantia nigra (SN), which is responsible for the core motor symptoms of PD. Currently, there is no cure for PD, and its prevalence is increasing, prompting the search for novel neuroprotective treatments. Neuroinflammation is a core pathological process in PD, evident by increased inflammatory biomarkers in the SN and cerebrospinal fluid. Interestingly, epidemiological studies have reported a reduced risk of PD in users of nonsteroidal anti-inflammatory drugs compared to non-users, suggesting the neuroprotective potential of anti-inflammatory drugs. Therefore, this study aimed to: (1) test the efficacy of novel oral formulations of edaravone (EDR) and curcumin (CUR) (which possess antiinflammatory and anti-oxidative properties) to alleviate motor and non-motor symptoms, and associated pathology in the intrastriatal lipopolysaccharide (LPS) model of PD; (2) investigate the expression of proteins linked to familial PD and markers of autophagy in the intrastriatal LPS model treated with EDR and CUR. Fifty-two C57BL/6 mice were divided into 4 groups, namely; (1) control + vehicle; (2) LPS + vehicle; (3) LPS + EDR (made in vehicle) and ( 4) LPS + CUR (made in vehicle). 10 µg of LPS was administered stereotaxically into the right striatum, and EDR and CUR treatments were initiated 2-weeks after the LPS injections. Behavioural tests were carried out at 4-and 8-weeks after LPS injection followed by tissue collection at 8-weeks. Intrastriatal administration of LPS induced motor deficits and anxiety-like behaviours at 4-and 8-weeks, which were accompanied by astroglial activation, increased protein expression of α-synuclein, heat shock cognate protein of 70 kDa (HSC-70) and Rab-10, and reduced levels of tyrosine hydroxylase (TH) protein in the striatum. Additionally, LPS induced astroglial activation in the olfactory bulb, along with changes in the protein expression of HSC-70. The changes associated with EDR and CUR in the striatum and olfactory bulb were not statistically significant compared to the LPS group. Intrastriatal administration of LPS induced pathological changes of PD such as motor deficits, reduced expression of TH protein and increased α-synuclein protein, as well as some alterations in proteins linked to familial PD and autophagy in the olfactory bulb and striatum, without pronounced therapeutic effects of EDR and CUR. Our results may suggest that EDR and CUR lack therapeutic effects when administered after the disease process was already initiated. Thus, our treatment regimen or the physicochemical properties of EDR and CUR could be further refined to elevate the therapeutic effects of these formulations.

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Self-nanomicellizing solid dispersion of edaravone: part I – oral bioavailability improvement

Cited by 26 publications

References 70 publications

Quality-by-Design Approach for the Development of Nano-Sized Tea Tree Oil Formulation-Impregnated Biocompatible Gel with Antimicrobial Properties

Quality-by-Design Approach for the Development of Nano-Sized Tea Tree Oil Formulation-Impregnated Biocompatible Gel with Antimicrobial Properties

A Novel Oral Edaravone Formulation Partially Alleviates Tau Pathology and Motor Deficits in an Animal Model of Frontotemporal Dementia

The Effects of Novel Formulations of Edaravone and Curcumin in the Mouse Intrastriatal Lipopolysaccharide Model of Parkinson’s Disease

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