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

Binyamin O, Larush L, Frid K, Keller G, Friedman-Levi Y, Ovadia H, Abramsky O, Magdassi S, Gabizon R - Int J Nanomedicine (2015)

Bottom Line: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system and is associated with demyelination, neurodegeneration, and sensitivity to oxidative stress.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.On the mechanistic side, our results demonstrate that lipid oxidation may be a seminal feature in both demyelination and neurodegeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The Agnes Ginges Center of Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Small Nano-PSO particles are inactive against EAE.Notes: Mice induced for EAE were treated with Nano-PSO in different droplet sizes. As shown in the insert, while one group of induced mice was left untreated (n=8), a second group was treated with 180 nm droplets of Nano-PSO (n=7), and a third group with 30 nm Nano-PSO droplets (n=7). P<0.05 for the untreated group versus the group treated with 180 nm droplets of Nano-PSO.Abbreviations: PSO, pomegranate seed oil; EAE, experimental autoimmune encephalomyelitis.
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f5-ijn-10-7165: Small Nano-PSO particles are inactive against EAE.Notes: Mice induced for EAE were treated with Nano-PSO in different droplet sizes. As shown in the insert, while one group of induced mice was left untreated (n=8), a second group was treated with 180 nm droplets of Nano-PSO (n=7), and a third group with 30 nm Nano-PSO droplets (n=7). P<0.05 for the untreated group versus the group treated with 180 nm droplets of Nano-PSO.Abbreviations: PSO, pomegranate seed oil; EAE, experimental autoimmune encephalomyelitis.

Mentions: Since the rational for using PSO nanodroplets in these experiments lies in the possibility that such entities, as opposed to the large drops of natural PSO, may escape the liver trap on their first passage, we next asked whether the size of such droplets is important. All batches of Nano-PSO in the previous experiments comprised droplets of 180 nm (Figure 1) since this size of nanoparticles was shown to be successful for other brain conditions.35,36 We now compared the α-EAE activity of the 180 nm nanodrops with that of a Nano-PSO formulation in which the average diameter of the droplets is close to 30 nm, a size used for the targeting of RNA and drugs containing lipid droplets to peripheral organs, such as liver37 or lungs.38 To prepare these 30 nm droplets formulation, a self-emulsifying system was developed according to the procedure described in the “Materials and methods” section and in patent No. 14/523,408.39 PSO nanodroplets of both sizes were administered to EAE-induced mice from day 1 of the induction at a dose of 10 μL of PSO per day. Figure 5 shows that the formulation comprising the lower size droplets had no beneficial effect in EAE-induced mice, as opposed to the strong response of the sick mice to the 180 nm formulation (P<0.05). The 30 nm formulation was even less active than the 10 μL dose of PSO in its natural form (Figure 1). It is possible that lower size nanodroplets may be absorbed by peripheral organs soon after ingestion and have no opportunity to pass the BBB from the blood and generate a beneficial effect in the CNS. Also, smaller droplets may be more prone to oxidation than the larger ones. Whether small Nano-PSO droplets can or cannot generate a beneficial effect in other clinical settings outside the brain remains to be established.


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

Binyamin O, Larush L, Frid K, Keller G, Friedman-Levi Y, Ovadia H, Abramsky O, Magdassi S, Gabizon R - Int J Nanomedicine (2015)

Small Nano-PSO particles are inactive against EAE.Notes: Mice induced for EAE were treated with Nano-PSO in different droplet sizes. As shown in the insert, while one group of induced mice was left untreated (n=8), a second group was treated with 180 nm droplets of Nano-PSO (n=7), and a third group with 30 nm Nano-PSO droplets (n=7). P<0.05 for the untreated group versus the group treated with 180 nm droplets of Nano-PSO.Abbreviations: PSO, pomegranate seed oil; EAE, experimental autoimmune encephalomyelitis.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664546&req=5

f5-ijn-10-7165: Small Nano-PSO particles are inactive against EAE.Notes: Mice induced for EAE were treated with Nano-PSO in different droplet sizes. As shown in the insert, while one group of induced mice was left untreated (n=8), a second group was treated with 180 nm droplets of Nano-PSO (n=7), and a third group with 30 nm Nano-PSO droplets (n=7). P<0.05 for the untreated group versus the group treated with 180 nm droplets of Nano-PSO.Abbreviations: PSO, pomegranate seed oil; EAE, experimental autoimmune encephalomyelitis.
Mentions: Since the rational for using PSO nanodroplets in these experiments lies in the possibility that such entities, as opposed to the large drops of natural PSO, may escape the liver trap on their first passage, we next asked whether the size of such droplets is important. All batches of Nano-PSO in the previous experiments comprised droplets of 180 nm (Figure 1) since this size of nanoparticles was shown to be successful for other brain conditions.35,36 We now compared the α-EAE activity of the 180 nm nanodrops with that of a Nano-PSO formulation in which the average diameter of the droplets is close to 30 nm, a size used for the targeting of RNA and drugs containing lipid droplets to peripheral organs, such as liver37 or lungs.38 To prepare these 30 nm droplets formulation, a self-emulsifying system was developed according to the procedure described in the “Materials and methods” section and in patent No. 14/523,408.39 PSO nanodroplets of both sizes were administered to EAE-induced mice from day 1 of the induction at a dose of 10 μL of PSO per day. Figure 5 shows that the formulation comprising the lower size droplets had no beneficial effect in EAE-induced mice, as opposed to the strong response of the sick mice to the 180 nm formulation (P<0.05). The 30 nm formulation was even less active than the 10 μL dose of PSO in its natural form (Figure 1). It is possible that lower size nanodroplets may be absorbed by peripheral organs soon after ingestion and have no opportunity to pass the BBB from the blood and generate a beneficial effect in the CNS. Also, smaller droplets may be more prone to oxidation than the larger ones. Whether small Nano-PSO droplets can or cannot generate a beneficial effect in other clinical settings outside the brain remains to be established.

Bottom Line: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system and is associated with demyelination, neurodegeneration, and sensitivity to oxidative stress.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.On the mechanistic side, our results demonstrate that lipid oxidation may be a seminal feature in both demyelination and neurodegeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The Agnes Ginges Center of Human Neurogenetics, Hadassah University Hospital, Jerusalem, Israel.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus