Pomegranate seed oil nanoemulsions for the prevention and treatment of neurodegenerative diseases: the case of genetic CJD

Mizrahi, Michal; Friedman-Levi, Yael; Larush, Liraz; Frid, Kati; Binyamin, Orli; Dori, Dvir; Fainstein, Nina; Ovadia, Haim; Ben‐Hur, Tamir; Magdassi, Shlomo; Gabizon, Ruth

doi:10.1016/j.nano.2014.03.015

Cited by 80 publications

(49 citation statements)

References 69 publications

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“…There are few reports showing PSO nanoemulsions preparation, employing different methods as sonication (Mizrahi et al 2014), self-nanoemulsifying (Lu et al 2015), ultrasonic emulsification/solvent evaporation (Baccarin & Lemos-Senna 2014;Baccarin et al 2015aBaccarin et al , 2015b. Recently, our group developed PSO nanoemulsion by nanoemulsification, employing pullulan as stabilizer (Ferreira et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Pomegranate seed oil nanoemulsions with selective antiglioma activity: optimization and evaluation of cytotoxicity, genotoxicity and oxidative effects on mononuclear cells

Ferreira

Gehrcke

Cervi

et al. 2016

Pharmaceutical Biology

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(2016) Pomegranate seed oil nanoemulsions with selective antiglioma activity: optimization and evaluation of cytotoxicity, genotoxicity and oxidative effects on mononuclear cells, Pharmaceutical Biology, 54:12, 2968-2977, DOI: 10.1080/13880209.2016 Context: Glioma is a malignant brain tumor with rapid proliferation, infiltrative growth, poor prognosis and it is chemoresistent. Pomegranate seed oil (PSO) has antioxidant, anti-inflammatory and antitumor properties. This study showed the optimization of PSO nanoemulsions (NEs) as an alternative for glioma treatment.Objective: The study aimed to evaluate PSO NEs cytotoxicity on human blood cells and antiglioma effects against C6 cells. Materials and methods: NEs were prepared by the spontaneous emulsification method, using PSO at 1.5 and 3.0%, and were evaluated regarding their physical stability and antioxidant activity. Toxicity evaluations in human blood cells were performed in terms of cell viability, genotoxicity, lipid peroxidation, protein carbonylation, catalase activity and hemolysis at 0.1, 0.25 and 0.5 mg/mL PSO, after a 72-h incubation period. In vitro antitumor effect was determined against glioma cells after 24 and 48 h, and astrocytes were used as a non-transformed cell model. Results: Formulations presented droplet size below 250 nm, low polydispersity index, negative zeta potential and pH in the acid range. NEs and PSO had scavenging capacity around 30% and promoted a proliferative effect in mononuclear cells, increasing about 50% cell viability. No genotoxic and oxidative damage was observed in lipid peroxidation, protein carbonylation and catalase activity evaluations for NEs. Hemolysis study showed a hemolytic effect at high concentrations. Moreover, formulations reduced only tumor cell viability to 47%, approximately. Discussion and conclusion: Formulations are adequate and safe for intravenous administration. Besides, in vitro antitumor activity indicates that NEs are promising for glioma treatment.ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Pomegranate seed oil nanoemulsions with selective antiglioma activity: optimization and evaluation of cytotoxicity, genotoxicity and oxidative effects on mononuclear cells

Ferreira

Gehrcke

Cervi

et al. 2016

Pharmaceutical Biology

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“…145 A pomegranate seed oil nanoemulsion with 135 nm particles was produced using the sonication technique and reduced lipid peroxidation and neuronal loss with strong protective effects. 146 Several other plant bioactive compounds have been studied using nanoemulsion delivery methods, such as a betlunic acid nanoemulsion with 200 nm particles produced by sonication and enhanced bioavailability. 147 A resveratrol nanoemulsion with 128 nm particles produced by high-speed homogenization enhanced bioavailability.…”

mentioning

confidence: 99%

Recent trends in the development of nanophytobioactive compounds and delivery systems for their possible role in reducing oxidative stress in Parkinson’s disease models

Ganesan¹,

Ko²,

Kim³

et al. 2015

IJN

102

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Oxidative stress plays a very critical role in neurodegenerative diseases, such as Parkinson’s disease (PD), which is the second most common neurodegenerative disease among elderly people worldwide. Increasing evidence has suggested that phytobioactive compounds show enhanced benefits in cell and animal models of PD. Curcumin, resveratrol, ginsenosides, quercetin, and catechin are phyto-derived bioactive compounds with important roles in the prevention and treatment of PD. However, in vivo studies suggest that their concentrations are very low to cross blood–brain barrier thereby it limits bioavailability, stability, and dissolution at target sites in the brain. To overcome these problems, nanophytomedicine with the controlled size of 1–100 nm is used to maximize efficiency in the treatment of PD. Nanosizing of phytobioactive compounds enhances the permeability into the brain with maximized efficiency and stability. Several nanodelivery techniques, including solid lipid nanoparticles, nanostructured lipid carriers, nanoliposomes, and nanoniosomes can be used for controlled delivery of nanobioactive compounds to brain. Nanocompounds, such as ginsenosides (19.9 nm) synthesized using a nanoemulsion technique, showed enhanced bioavailability in the rat brain. Here, we discuss the most recent trends and applications in PD, including 1) the role of phytobioactive compounds in reducing oxidative stress and their bioavailability; 2) the role of nanotechnology in reducing oxidative stress during PD; 3) nanodelivery systems; and 4) various nanophytobioactive compounds and their role in PD.

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“…49 In addition to demyelinating diseases, oxidative stress is also an important feature of most neurodegenerative conditions. 6,14 Indeed, the EO6 antibody shown here to stain plaques in the untreated EAE brains as it was shown to mark human MS plaques 6 also reacts extensively with brain slices from TgMHu2ME199K mice, a mouse model of genetic prion disease, 17 suggesting that lipid oxidation may be a general feature of neurodegeneration. Most importantly, Nano-PSO was also beneficial in the prevention and treatment of genetic prion disease in the TgMHu2ME199K model, indicating that reagents that can prevent lipid oxidation may be beneficial for an array of neurodegenerative diseases.…”

mentioning

confidence: 71%

“…6,16 We have recently shown that administration of a nanodroplet formulation of pomegranate seed oil (PSO), denominated Nano-PSO, can significantly reduce the oxidation of lipids in a transgenic mouse model of genetic prion disease. 17 In the TgMHu2ME199K mice, reduction in lipid oxidation, as well as reduced neuronal death, occurred concomitantly with a significant delay in disease onset, constituting a proof of concept that an advanced formulation of a natural antioxidant may fight neurodegeneration. No apparent side effects were observed in the time frame (6-8 months) and doses of Nano-PSO administered to the mice in these experiments.…”

Section: Introductionmentioning

confidence: 97%

Treatment of a multiple sclerosis animal model by a novel nanodrop formulation of a natural antioxidant

Binyamin¹,

Larush²,

Frid³

et al. 2015

IJN

Self Cite

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Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system and is associated with demyelination, neurodegeneration, and sensitivity to oxidative stress. In this work, we administered a nanodroplet formulation of pomegranate seed oil (PSO), denominated Nano-PSO, to mice induced for experimental autoimmune encephalomyelitis (EAE), an established model of MS. PSO comprises high levels of punicic acid, a unique polyunsaturated fatty acid considered as one of the strongest natural antioxidants. We show here that while EAE-induced mice treated with natural PSO presented some reduction in disease burden, this beneficial effect increased significantly when EAE mice were treated with Nano-PSO of specific size nanodroplets at much lower concentrations of the oil. Pathological examinations revealed that Nano-PSO administration dramatically reduced demyelination and oxidation of lipids in the brains of the affected animals, which are hallmarks of this severe neurological disease. We propose that novel formulations of natural antioxidants such as Nano-PSO may be considered for the treatment of patients suffering from demyelinating diseases. On the mechanistic side, our results demonstrate that lipid oxidation may be a seminal feature in both demyelination and neurodegeneration.

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Pomegranate seed oil nanoemulsions for the prevention and treatment of neurodegenerative diseases: the case of genetic CJD

Cited by 80 publications

References 69 publications

Pomegranate seed oil nanoemulsions with selective antiglioma activity: optimization and evaluation of cytotoxicity, genotoxicity and oxidative effects on mononuclear cells

Pomegranate seed oil nanoemulsions with selective antiglioma activity: optimization and evaluation of cytotoxicity, genotoxicity and oxidative effects on mononuclear cells

Recent trends in the development of nanophytobioactive compounds and delivery systems for their possible role in reducing oxidative stress in Parkinson’s disease models

Treatment of a multiple sclerosis animal model by a novel nanodrop formulation of a natural antioxidant

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Pomegranate seed oil nanoemulsions for the prevention and treatment of neurodegenerative diseases: the case of genetic CJD

Cited by 80 publications

References 69 publications

Pomegranate seed oil nanoemulsions with selective antiglioma activity: optimization and evaluation of cytotoxicity, genotoxicity and oxidative effects on mononuclear cells

Pomegranate seed oil nanoemulsions with selective antiglioma activity: optimization and evaluation of cytotoxicity, genotoxicity and oxidative effects on mononuclear cells

Recent trends in the development of nanophytobioactive compounds and delivery systems for their possible role in reducing oxidative stress in Parkinson&rsquo;s disease models

Treatment of a multiple sclerosis animal model by a novel nanodrop formulation of a natural antioxidant

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Recent trends in the development of nanophytobioactive compounds and delivery systems for their possible role in reducing oxidative stress in Parkinson’s disease models