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Comparative Studies of the Uptake and Internalization Pathways of Different Lipid Nano-Systems Intended for Brain Delivery

Lipid nano-systems were prepared and characterized in a series of well-established in vitro tests that could assess their interactions with the hCMEC/D3 and SH-SY5Y cell lines as a model for the blood–brain barrier and neuronal function, accordingly. The prepared formulations of nanoliposomes and na...

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Autores principales: Mihailova, Ljubica, Shalabalija, Dushko, Zimmer, Andreas, Geskovski, Nikola, Makreski, Petre, Petrushevska, Marija, Simonoska Crcarevska, Maja, Glavas Dodov, Marija
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458318/
https://www.ncbi.nlm.nih.gov/pubmed/37631296
http://dx.doi.org/10.3390/pharmaceutics15082082
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author Mihailova, Ljubica
Shalabalija, Dushko
Zimmer, Andreas
Geskovski, Nikola
Makreski, Petre
Petrushevska, Marija
Simonoska Crcarevska, Maja
Glavas Dodov, Marija
author_facet Mihailova, Ljubica
Shalabalija, Dushko
Zimmer, Andreas
Geskovski, Nikola
Makreski, Petre
Petrushevska, Marija
Simonoska Crcarevska, Maja
Glavas Dodov, Marija
author_sort Mihailova, Ljubica
collection PubMed
description Lipid nano-systems were prepared and characterized in a series of well-established in vitro tests that could assess their interactions with the hCMEC/D3 and SH-SY5Y cell lines as a model for the blood–brain barrier and neuronal function, accordingly. The prepared formulations of nanoliposomes and nanostructured lipid carriers were characterized by z-average diameters of ~120 nm and ~105 nm, respectively, following a unimodal particle size distribution (PDI < 0.3) and negative Z-potential (−24.30 mV to −31.20 mV). Stability studies implied that the nano-systems were stable in a physiologically relevant medium as well as human plasma, except nanoliposomes containing poloxamer on their surface, where there was an increase in particle size of ~26%. The presence of stealth polymer tends to decrease the amount of adsorbed proteins onto a particle’s surface, according to protein adsorption studies. Both formulations of nanoliposomes were characterized by a low cytotoxicity, while their cell viability was reduced when incubated with the highest concentration (100 μg/mL) of nanostructured lipid formulations, which could have been associated with the consumption of cellular energy, thus resulting in a reduction in metabolic active cells. The uptake of all the nano-systems in the hCMEC/D3 and SH-SY5Y cell lines was successful, most likely following ATP-dependent internalization, as well as transport via passive diffusion.
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spelling pubmed-104583182023-08-27 Comparative Studies of the Uptake and Internalization Pathways of Different Lipid Nano-Systems Intended for Brain Delivery Mihailova, Ljubica Shalabalija, Dushko Zimmer, Andreas Geskovski, Nikola Makreski, Petre Petrushevska, Marija Simonoska Crcarevska, Maja Glavas Dodov, Marija Pharmaceutics Article Lipid nano-systems were prepared and characterized in a series of well-established in vitro tests that could assess their interactions with the hCMEC/D3 and SH-SY5Y cell lines as a model for the blood–brain barrier and neuronal function, accordingly. The prepared formulations of nanoliposomes and nanostructured lipid carriers were characterized by z-average diameters of ~120 nm and ~105 nm, respectively, following a unimodal particle size distribution (PDI < 0.3) and negative Z-potential (−24.30 mV to −31.20 mV). Stability studies implied that the nano-systems were stable in a physiologically relevant medium as well as human plasma, except nanoliposomes containing poloxamer on their surface, where there was an increase in particle size of ~26%. The presence of stealth polymer tends to decrease the amount of adsorbed proteins onto a particle’s surface, according to protein adsorption studies. Both formulations of nanoliposomes were characterized by a low cytotoxicity, while their cell viability was reduced when incubated with the highest concentration (100 μg/mL) of nanostructured lipid formulations, which could have been associated with the consumption of cellular energy, thus resulting in a reduction in metabolic active cells. The uptake of all the nano-systems in the hCMEC/D3 and SH-SY5Y cell lines was successful, most likely following ATP-dependent internalization, as well as transport via passive diffusion. MDPI 2023-08-03 /pmc/articles/PMC10458318/ /pubmed/37631296 http://dx.doi.org/10.3390/pharmaceutics15082082 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mihailova, Ljubica
Shalabalija, Dushko
Zimmer, Andreas
Geskovski, Nikola
Makreski, Petre
Petrushevska, Marija
Simonoska Crcarevska, Maja
Glavas Dodov, Marija
Comparative Studies of the Uptake and Internalization Pathways of Different Lipid Nano-Systems Intended for Brain Delivery
title Comparative Studies of the Uptake and Internalization Pathways of Different Lipid Nano-Systems Intended for Brain Delivery
title_full Comparative Studies of the Uptake and Internalization Pathways of Different Lipid Nano-Systems Intended for Brain Delivery
title_fullStr Comparative Studies of the Uptake and Internalization Pathways of Different Lipid Nano-Systems Intended for Brain Delivery
title_full_unstemmed Comparative Studies of the Uptake and Internalization Pathways of Different Lipid Nano-Systems Intended for Brain Delivery
title_short Comparative Studies of the Uptake and Internalization Pathways of Different Lipid Nano-Systems Intended for Brain Delivery
title_sort comparative studies of the uptake and internalization pathways of different lipid nano-systems intended for brain delivery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458318/
https://www.ncbi.nlm.nih.gov/pubmed/37631296
http://dx.doi.org/10.3390/pharmaceutics15082082
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