Development of Liposomes That Target Axon Terminals Encapsulating Berberine in Cultured Primary Neurons

Most of the energy in neurons is produced in mitochondria. Mitochondria generate the ATP that is essential for neuronal growth, function, and regeneration. Mitochondrial axonal transport plays a crucial role in maintaining neuronal homeostasis and biological activity. Decreased mitochondrial axonal...

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Main Authors: Ikuma Hori, Hideyoshi Harashima, Yuma Yamada
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/16/1/49
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author Ikuma Hori
Hideyoshi Harashima
Yuma Yamada
author_facet Ikuma Hori
Hideyoshi Harashima
Yuma Yamada
author_sort Ikuma Hori
collection DOAJ
description Most of the energy in neurons is produced in mitochondria. Mitochondria generate the ATP that is essential for neuronal growth, function, and regeneration. Mitochondrial axonal transport plays a crucial role in maintaining neuronal homeostasis and biological activity. Decreased mitochondrial axonal transport at axon terminals, where the metabolism of substances is likely to be delayed, may contribute to neurological dysfunction. Therefore, regulation of mitochondrial dynamics at axon terminals has attracted considerable interest as a strategy to modulate neuronal function. Nanoparticles may be useful in controlling local mitochondrial dynamics. Nevertheless, there are few reports on the influence of drug delivery that nanoparticles impart on the mitochondrial dynamics in neurons. This paper reports the results of a study using liposomes (LPs) to examine local drug delivery and pharmacological actions on neurons. We tested berberine (BBR), which is an activator of AMP-activated protein kinase (AMPK), to examine the utility of this drug as a cellular energy sensor. Axon terminals targeting LPs were prepared. The amount of axon terminals targeting LPs was increased compared with treatment using cationic LPs. Moreover, axon terminal-targeting LPs increased anterograde transport by about 40% compared with that of either naked BBR or cationic LPs and suppressed axonal retraction. Our findings suggest that local drug delivery to neurons is important for enhancing pharmacological activity in axon terminals.
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spelling doaj.art-4bf2dd18a6954d9e93c45d8d666d47962024-01-26T18:06:23ZengMDPI AGPharmaceutics1999-49232023-12-011614910.3390/pharmaceutics16010049Development of Liposomes That Target Axon Terminals Encapsulating Berberine in Cultured Primary NeuronsIkuma Hori0Hideyoshi Harashima1Yuma Yamada2Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo 060-0812, JapanFaculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, JapanFaculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, JapanMost of the energy in neurons is produced in mitochondria. Mitochondria generate the ATP that is essential for neuronal growth, function, and regeneration. Mitochondrial axonal transport plays a crucial role in maintaining neuronal homeostasis and biological activity. Decreased mitochondrial axonal transport at axon terminals, where the metabolism of substances is likely to be delayed, may contribute to neurological dysfunction. Therefore, regulation of mitochondrial dynamics at axon terminals has attracted considerable interest as a strategy to modulate neuronal function. Nanoparticles may be useful in controlling local mitochondrial dynamics. Nevertheless, there are few reports on the influence of drug delivery that nanoparticles impart on the mitochondrial dynamics in neurons. This paper reports the results of a study using liposomes (LPs) to examine local drug delivery and pharmacological actions on neurons. We tested berberine (BBR), which is an activator of AMP-activated protein kinase (AMPK), to examine the utility of this drug as a cellular energy sensor. Axon terminals targeting LPs were prepared. The amount of axon terminals targeting LPs was increased compared with treatment using cationic LPs. Moreover, axon terminal-targeting LPs increased anterograde transport by about 40% compared with that of either naked BBR or cationic LPs and suppressed axonal retraction. Our findings suggest that local drug delivery to neurons is important for enhancing pharmacological activity in axon terminals.https://www.mdpi.com/1999-4923/16/1/49liposomeaxon terminalsmitochondrial dynamicsaxon outgrowth
spellingShingle Ikuma Hori
Hideyoshi Harashima
Yuma Yamada
Development of Liposomes That Target Axon Terminals Encapsulating Berberine in Cultured Primary Neurons
Pharmaceutics
liposome
axon terminals
mitochondrial dynamics
axon outgrowth
title Development of Liposomes That Target Axon Terminals Encapsulating Berberine in Cultured Primary Neurons
title_full Development of Liposomes That Target Axon Terminals Encapsulating Berberine in Cultured Primary Neurons
title_fullStr Development of Liposomes That Target Axon Terminals Encapsulating Berberine in Cultured Primary Neurons
title_full_unstemmed Development of Liposomes That Target Axon Terminals Encapsulating Berberine in Cultured Primary Neurons
title_short Development of Liposomes That Target Axon Terminals Encapsulating Berberine in Cultured Primary Neurons
title_sort development of liposomes that target axon terminals encapsulating berberine in cultured primary neurons
topic liposome
axon terminals
mitochondrial dynamics
axon outgrowth
url https://www.mdpi.com/1999-4923/16/1/49
work_keys_str_mv AT ikumahori developmentofliposomesthattargetaxonterminalsencapsulatingberberineinculturedprimaryneurons
AT hideyoshiharashima developmentofliposomesthattargetaxonterminalsencapsulatingberberineinculturedprimaryneurons
AT yumayamada developmentofliposomesthattargetaxonterminalsencapsulatingberberineinculturedprimaryneurons