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Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson's disease.

Herrán E, Requejo C, Ruiz-Ortega JA, Aristieta A, Igartua M, Bengoetxea H, Ugedo L, Pedraz JL, Lafuente JV, Hernández RM - Int J Nanomedicine (2014)

Bottom Line: The NS particle size was about 200 nm and the simultaneous addition of VEGF NS and GDNF NS resulted in significant protection of the PC-12 cell line against 6-OHDA in vitro.The results showed that VEGF NS and GDNF NS significantly decreased the number of amphetamine-induced rotations at the end of the study.In addition, tyrosine hydroxylase immunohistochemical analysis in the striatum and the external substantia nigra confirmed a significant enhancement of neurons in the VEGF NS and GDNF NS treatment group.

View Article: PubMed Central - PubMed

Affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, University of the Basque Country (UPV/EHU), School of Pharmacy, Vitoria, Spain ; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria, Spain.

ABSTRACT
Current research efforts are focused on the application of growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), as neuroregenerative approaches that will prevent the neurodegenerative process in Parkinson's disease. Continuing a previous work published by our research group, and with the aim to overcome different limitations related to growth factor administration, VEGF and GDNF were encapsulated in poly(lactic-co-glycolic acid) nanospheres (NS). This strategy facilitates the combined administration of the VEGF and GDNF into the brain of 6-hydroxydopamine (6-OHDA) partially lesioned rats, resulting in a continuous and simultaneous drug release. The NS particle size was about 200 nm and the simultaneous addition of VEGF NS and GDNF NS resulted in significant protection of the PC-12 cell line against 6-OHDA in vitro. Once the poly(lactic-co-glycolic acid) NS were implanted into the striatum of 6-OHDA partially lesioned rats, the amphetamine rotation behavior test was carried out over 10 weeks, in order to check for in vivo efficacy. The results showed that VEGF NS and GDNF NS significantly decreased the number of amphetamine-induced rotations at the end of the study. In addition, tyrosine hydroxylase immunohistochemical analysis in the striatum and the external substantia nigra confirmed a significant enhancement of neurons in the VEGF NS and GDNF NS treatment group. The synergistic effect of VEGF NS and GDNF NS allows for a reduction of the dose by half, and may be a valuable neurogenerative/neuroreparative approach for treating Parkinson's disease.

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Related in: MedlinePlus

GDNF NS and VEGF NS characterization and in vitro toxicity study.Notes: (A) Scanning electron microscope (SEM) photomicrographs of GDNF NS and VEGF NS. (B) The in vitro VEGF NS and GDNF NS release profiles at 37°C in phosphate-buffered saline (pH 7.4). The results are represented as the mean ± standard deviation (n=3).Abbreviations: GDNF, glial cell line-derived neurotrophic factor; NS, nanospheres; VEGF, vascular endothelial growth factor.
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f2-ijn-9-2677: GDNF NS and VEGF NS characterization and in vitro toxicity study.Notes: (A) Scanning electron microscope (SEM) photomicrographs of GDNF NS and VEGF NS. (B) The in vitro VEGF NS and GDNF NS release profiles at 37°C in phosphate-buffered saline (pH 7.4). The results are represented as the mean ± standard deviation (n=3).Abbreviations: GDNF, glial cell line-derived neurotrophic factor; NS, nanospheres; VEGF, vascular endothelial growth factor.

Mentions: NS presented particle sizes of around 235.6±0.111 nm for VEGF NS, 221.1±0.065 nm for GDNF NS, and 267.00±0.111 nm for empty NS. The zeta potential was similar for all the formulations, around −25 mV. When visualized by scanning electron microscopy, the NS showed a spherical shape without irregularities (Figure 2). The encapsulation efficiency (EE) was 44% for VEGF NS and was higher for GDNF NS, at 74% (Figure 2A and Table 1). Both formulations had similar percentages of surface-associated protein (approximately 23%) and similar in vitro release profiles. Figure 2B shows that VEGF and GDNF released from PLGA NS presented similar release profiles, with an initial burst release of 28%±0.5% of the total loaded protein in the first 24 hours, and a second continuous release rate of 1 ng/day/mg persisting until the end of the assay.


Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson's disease.

Herrán E, Requejo C, Ruiz-Ortega JA, Aristieta A, Igartua M, Bengoetxea H, Ugedo L, Pedraz JL, Lafuente JV, Hernández RM - Int J Nanomedicine (2014)

GDNF NS and VEGF NS characterization and in vitro toxicity study.Notes: (A) Scanning electron microscope (SEM) photomicrographs of GDNF NS and VEGF NS. (B) The in vitro VEGF NS and GDNF NS release profiles at 37°C in phosphate-buffered saline (pH 7.4). The results are represented as the mean ± standard deviation (n=3).Abbreviations: GDNF, glial cell line-derived neurotrophic factor; NS, nanospheres; VEGF, vascular endothelial growth factor.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4043720&req=5

f2-ijn-9-2677: GDNF NS and VEGF NS characterization and in vitro toxicity study.Notes: (A) Scanning electron microscope (SEM) photomicrographs of GDNF NS and VEGF NS. (B) The in vitro VEGF NS and GDNF NS release profiles at 37°C in phosphate-buffered saline (pH 7.4). The results are represented as the mean ± standard deviation (n=3).Abbreviations: GDNF, glial cell line-derived neurotrophic factor; NS, nanospheres; VEGF, vascular endothelial growth factor.
Mentions: NS presented particle sizes of around 235.6±0.111 nm for VEGF NS, 221.1±0.065 nm for GDNF NS, and 267.00±0.111 nm for empty NS. The zeta potential was similar for all the formulations, around −25 mV. When visualized by scanning electron microscopy, the NS showed a spherical shape without irregularities (Figure 2). The encapsulation efficiency (EE) was 44% for VEGF NS and was higher for GDNF NS, at 74% (Figure 2A and Table 1). Both formulations had similar percentages of surface-associated protein (approximately 23%) and similar in vitro release profiles. Figure 2B shows that VEGF and GDNF released from PLGA NS presented similar release profiles, with an initial burst release of 28%±0.5% of the total loaded protein in the first 24 hours, and a second continuous release rate of 1 ng/day/mg persisting until the end of the assay.

Bottom Line: The NS particle size was about 200 nm and the simultaneous addition of VEGF NS and GDNF NS resulted in significant protection of the PC-12 cell line against 6-OHDA in vitro.The results showed that VEGF NS and GDNF NS significantly decreased the number of amphetamine-induced rotations at the end of the study.In addition, tyrosine hydroxylase immunohistochemical analysis in the striatum and the external substantia nigra confirmed a significant enhancement of neurons in the VEGF NS and GDNF NS treatment group.

View Article: PubMed Central - PubMed

Affiliation: NanoBioCel Group, Laboratory of Pharmaceutics, University of the Basque Country (UPV/EHU), School of Pharmacy, Vitoria, Spain ; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria, Spain.

ABSTRACT
Current research efforts are focused on the application of growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), as neuroregenerative approaches that will prevent the neurodegenerative process in Parkinson's disease. Continuing a previous work published by our research group, and with the aim to overcome different limitations related to growth factor administration, VEGF and GDNF were encapsulated in poly(lactic-co-glycolic acid) nanospheres (NS). This strategy facilitates the combined administration of the VEGF and GDNF into the brain of 6-hydroxydopamine (6-OHDA) partially lesioned rats, resulting in a continuous and simultaneous drug release. The NS particle size was about 200 nm and the simultaneous addition of VEGF NS and GDNF NS resulted in significant protection of the PC-12 cell line against 6-OHDA in vitro. Once the poly(lactic-co-glycolic acid) NS were implanted into the striatum of 6-OHDA partially lesioned rats, the amphetamine rotation behavior test was carried out over 10 weeks, in order to check for in vivo efficacy. The results showed that VEGF NS and GDNF NS significantly decreased the number of amphetamine-induced rotations at the end of the study. In addition, tyrosine hydroxylase immunohistochemical analysis in the striatum and the external substantia nigra confirmed a significant enhancement of neurons in the VEGF NS and GDNF NS treatment group. The synergistic effect of VEGF NS and GDNF NS allows for a reduction of the dose by half, and may be a valuable neurogenerative/neuroreparative approach for treating Parkinson's disease.

Show MeSH
Related in: MedlinePlus