GDNF mimetics delivery by porous silicon nanoparticles for improved Parkinson’s disease management

Wei Li, Ermei Mäkilä, Jarno Salonen, Mart Saarma, Yulia Sidorova, Helder Almeida Santos

Tutkimustuotos: KonferenssimateriaalitKonferenssiesitys

Kuvaus

Parkinson’s disease is neurodegenerative movement disorder caused by
progressive degeneration of dopaminergic neurons in substantia nigra. Currently, there are no treatments to slow down, stop or reverse the loss of dopaminergic neuros. Glial cell line-derived neurotrophic factor (GDNF) is a protein that has been shown to prevent the death and help to repair the damaged neurons. However, GDNF is a large molecule (about 32 kDa) that cannot cross the blood brain barrier (BBB), and therefore needs to be delivered by intracranial administration, which requires complex and expensive stereotactic surgery. Generally, small molecules are easier to across the BBB than large
molecules. Thus, small molecules with similar biological activity to GDNF
(named GDNF mimetics) might be a better approach to translate into the clinic.
Several GDNF mimetics (molecular weight 500-600 g/mol), which are able to activate GDNF receptors and support the survival of dopaminergic neurons, have been found, but they have limited aqueous solubility. Porous silicon nanoparticles (PSi NPs) have the ability to improve the solubility and dissolution rate of poorly water-soluble drugs, as well as to enhance the drug permeation across biological barriers. In our study,
GDNF mimetics were loaded into thermally oxidized-PSi (TOPSi) NPs, by which the solubility and dissolution rate of GDNF mimetics were considerably enhanced. Luciferase assay, GDNF receptor RET phosphorylation and internal signalling assay showed that the GDNF mimetics delivered by the TOPSi NPs exhibit higher activity than pristine GDNF mimetics, even in the absence of organic solvents.
Alkuperäiskielienglanti
Sivut1848
Sivumäärä1
DOI - pysyväislinkit
TilaJulkaistu - heinäkuuta 2018
OKM-julkaisutyyppiEi sovellu

Tieteenalat

  • 3112 Neurotieteet

Lainaa tätä

@conference{430dac9e1fd74312ac0fb864d852d7ef,
title = "GDNF mimetics delivery by porous silicon nanoparticles for improved Parkinson’s disease management",
abstract = "Parkinson’s disease is neurodegenerative movement disorder caused byprogressive degeneration of dopaminergic neurons in substantia nigra. Currently, there are no treatments to slow down, stop or reverse the loss of dopaminergic neuros. Glial cell line-derived neurotrophic factor (GDNF) is a protein that has been shown to prevent the death and help to repair the damaged neurons. However, GDNF is a large molecule (about 32 kDa) that cannot cross the blood brain barrier (BBB), and therefore needs to be delivered by intracranial administration, which requires complex and expensive stereotactic surgery. Generally, small molecules are easier to across the BBB than largemolecules. Thus, small molecules with similar biological activity to GDNF(named GDNF mimetics) might be a better approach to translate into the clinic.Several GDNF mimetics (molecular weight 500-600 g/mol), which are able to activate GDNF receptors and support the survival of dopaminergic neurons, have been found, but they have limited aqueous solubility. Porous silicon nanoparticles (PSi NPs) have the ability to improve the solubility and dissolution rate of poorly water-soluble drugs, as well as to enhance the drug permeation across biological barriers. In our study,GDNF mimetics were loaded into thermally oxidized-PSi (TOPSi) NPs, by which the solubility and dissolution rate of GDNF mimetics were considerably enhanced. Luciferase assay, GDNF receptor RET phosphorylation and internal signalling assay showed that the GDNF mimetics delivered by the TOPSi NPs exhibit higher activity than pristine GDNF mimetics, even in the absence of organic solvents.",
keywords = "3112 Neurosciences",
author = "Wei Li and Ermei M{\"a}kil{\"a} and Jarno Salonen and Mart Saarma and Yulia Sidorova and {Almeida Santos}, Helder",
year = "2018",
month = "7",
doi = "10.1016/j.nano.2017.11.290",
language = "English",
pages = "1848",

}

GDNF mimetics delivery by porous silicon nanoparticles for improved Parkinson’s disease management. / Li, Wei; Mäkilä, Ermei; Salonen, Jarno; Saarma, Mart; Sidorova, Yulia; Almeida Santos, Helder.

2018. 1848.

Tutkimustuotos: KonferenssimateriaalitKonferenssiesitys

TY - CONF

T1 - GDNF mimetics delivery by porous silicon nanoparticles for improved Parkinson’s disease management

AU - Li, Wei

AU - Mäkilä, Ermei

AU - Salonen, Jarno

AU - Saarma, Mart

AU - Sidorova, Yulia

AU - Almeida Santos, Helder

PY - 2018/7

Y1 - 2018/7

N2 - Parkinson’s disease is neurodegenerative movement disorder caused byprogressive degeneration of dopaminergic neurons in substantia nigra. Currently, there are no treatments to slow down, stop or reverse the loss of dopaminergic neuros. Glial cell line-derived neurotrophic factor (GDNF) is a protein that has been shown to prevent the death and help to repair the damaged neurons. However, GDNF is a large molecule (about 32 kDa) that cannot cross the blood brain barrier (BBB), and therefore needs to be delivered by intracranial administration, which requires complex and expensive stereotactic surgery. Generally, small molecules are easier to across the BBB than largemolecules. Thus, small molecules with similar biological activity to GDNF(named GDNF mimetics) might be a better approach to translate into the clinic.Several GDNF mimetics (molecular weight 500-600 g/mol), which are able to activate GDNF receptors and support the survival of dopaminergic neurons, have been found, but they have limited aqueous solubility. Porous silicon nanoparticles (PSi NPs) have the ability to improve the solubility and dissolution rate of poorly water-soluble drugs, as well as to enhance the drug permeation across biological barriers. In our study,GDNF mimetics were loaded into thermally oxidized-PSi (TOPSi) NPs, by which the solubility and dissolution rate of GDNF mimetics were considerably enhanced. Luciferase assay, GDNF receptor RET phosphorylation and internal signalling assay showed that the GDNF mimetics delivered by the TOPSi NPs exhibit higher activity than pristine GDNF mimetics, even in the absence of organic solvents.

AB - Parkinson’s disease is neurodegenerative movement disorder caused byprogressive degeneration of dopaminergic neurons in substantia nigra. Currently, there are no treatments to slow down, stop or reverse the loss of dopaminergic neuros. Glial cell line-derived neurotrophic factor (GDNF) is a protein that has been shown to prevent the death and help to repair the damaged neurons. However, GDNF is a large molecule (about 32 kDa) that cannot cross the blood brain barrier (BBB), and therefore needs to be delivered by intracranial administration, which requires complex and expensive stereotactic surgery. Generally, small molecules are easier to across the BBB than largemolecules. Thus, small molecules with similar biological activity to GDNF(named GDNF mimetics) might be a better approach to translate into the clinic.Several GDNF mimetics (molecular weight 500-600 g/mol), which are able to activate GDNF receptors and support the survival of dopaminergic neurons, have been found, but they have limited aqueous solubility. Porous silicon nanoparticles (PSi NPs) have the ability to improve the solubility and dissolution rate of poorly water-soluble drugs, as well as to enhance the drug permeation across biological barriers. In our study,GDNF mimetics were loaded into thermally oxidized-PSi (TOPSi) NPs, by which the solubility and dissolution rate of GDNF mimetics were considerably enhanced. Luciferase assay, GDNF receptor RET phosphorylation and internal signalling assay showed that the GDNF mimetics delivered by the TOPSi NPs exhibit higher activity than pristine GDNF mimetics, even in the absence of organic solvents.

KW - 3112 Neurosciences

U2 - 10.1016/j.nano.2017.11.290

DO - 10.1016/j.nano.2017.11.290

M3 - Paper

SP - 1848

ER -