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3 results on '"Controlled transport of fragile therapeutic proteins"'

1. Novel design of (PEG-ylated)PAMAM-based nanoparticles for sustained delivery of BDNF to neurotoxin-injured differentiated neuroblastoma cells

Author

Maria Dąbkowska, Karolina Łuczkowska, Dorota Rogińska, Anna Sobuś, Monika Wasilewska, Zofia Ulańczyk, and Bogusław Machaliński

Subjects
Brain-derived neurotrophic factor (BDNF), Poly(amidoamine) dendrimers (PAMAM), Neurotoxin-treated neuroblastoma cells, Model of neurodegenerative mechanisms, Nanoparticles encapsulated in polyethylene glycol (PEG), Controlled transport of fragile therapeutic proteins, Biotechnology, TP248.13-248.65, Medical technology, R855-855.5
Abstract

Abstract Brain-derived neurotrophic factor (BDNF) is essential for the development and function of human neurons, therefore it is a promising target for neurodegenerative disorders treatment. Here, we studied BDNF-based electrostatic complex with dendrimer nanoparticles encapsulated in polyethylene glycol (PEG) in neurotoxin-treated, differentiated neuroblastoma SH-SY5Y cells, a model of neurodegenerative mechanisms. PEG layer was adsorbed at dendrimer-protein core nanoparticles to decrease their cellular uptake and to reduce BDNF-other proteins interactions for a prolonged time. Cytotoxicity and confocal microscopy analysis revealed PEG-ylated BDNF-dendrimer nanoparticles can be used for continuous neurotrophic factor delivery to the neurotoxin-treated cells over 24 h without toxic effect. We offer a reliable electrostatic route for efficient encapsulation and controlled transport of fragile therapeutic proteins without any covalent cross-linker; this could be considered as a safe drug delivery system. Understanding the polyvalent BDNF interactions with dendrimer core nanoparticles offers new possibilities for design of well-ordered protein drug delivery systems.

Published
2020
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3. Novel design of (PEG-ylated)PAMAM-based nanoparticles for sustained delivery of BDNF to neurotoxin-injured differentiated neuroblastoma cells

Author

Karolina Łuczkowska, Anna Sobuś, Zofia Ulańczyk, Bogusław Machaliński, Monika Wasilewska, Dorota Rogińska, and Maria Dąbkowska

Subjects
Dendrimers, lcsh:Medical technology, lcsh:Biotechnology, Poly(amidoamine) dendrimers (PAMAM), Neurotoxins, Static Electricity, Biomedical Engineering, Pharmaceutical Science, Medicine (miscellaneous), Bioengineering, 02 engineering and technology, Polyethylene glycol, Model of neurodegenerative mechanisms, 010402 general chemistry, Neurotoxin-treated neuroblastoma cells, 01 natural sciences, Applied Microbiology and Biotechnology, law.invention, Polyethylene Glycols, chemistry.chemical_compound, Neuroblastoma, Controlled transport of fragile therapeutic proteins, Neurotrophic factors, Confocal microscopy, law, Dendrimer, lcsh:TP248.13-248.65, Cell Line, Tumor, PEG ratio, Neurotoxin, Humans, Cytotoxicity, Drug Carriers, Chemistry, Research, Brain-Derived Neurotrophic Factor, Nanoparticles encapsulated in polyethylene glycol (PEG), 021001 nanoscience & nanotechnology, 0104 chemical sciences, lcsh:R855-855.5, Drug delivery, Biophysics, Molecular Medicine, Nanoparticles, Brain-derived neurotrophic factor (BDNF), 0210 nano-technology
Abstract

Brain-derived neurotrophic factor (BDNF) is essential for the development and function of human neurons, therefore it is a promising target for neurodegenerative disorders treatment. Here, we studied BDNF-based electrostatic complex with dendrimer nanoparticles encapsulated in polyethylene glycol (PEG) in neurotoxin-treated, differentiated neuroblastoma SH-SY5Y cells, a model of neurodegenerative mechanisms. PEG layer was adsorbed at dendrimer-protein core nanoparticles to decrease their cellular uptake and to reduce BDNF-other proteins interactions for a prolonged time. Cytotoxicity and confocal microscopy analysis revealed PEG-ylated BDNF-dendrimer nanoparticles can be used for continuous neurotrophic factor delivery to the neurotoxin-treated cells over 24 hours without toxic effect. We offer a reliable electrostatic route for efficient encapsulation and controlled transport of fragile therapeutic proteins without any covalent cross-linker; this could be considered as a safe drug delivery system. Understanding the polyvalent BDNF interactions with dendrimer core nanoparticles offers new possibilities for design of well-ordered protein drug delivery systems.

Published
2020

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