Cargando…

Cannabidiol-Loaded Extracellular Vesicles from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Paclitaxel-Induced Peripheral Neuropathy

In cancer patients, chronic paclitaxel (PTX) treatment causes excruciating pain, limiting its use in cancer chemotherapy. The neuroprotective potential of synthetic cannabidiol (CBD) and CBD formulated in extracellular vesicles (CBD-EVs) isolated from human umbilical cord derived mesenchymal stem ce...

Descripción completa

Detalles Bibliográficos
Autores principales: Kalvala, Anil Kumar, Bagde, Arvind, Arthur, Peggy, Kulkarni, Tanmay, Bhattacharya, Santanu, Surapaneni, Sunil, Patel, Nil Kumar, Nimma, Ramesh, Gebeyehu, Aragaw, Kommineni, Nagavendra, Meckes, Jr., David G., Sun, Li, Banjara, Bipika, Mosley-Kellum, Keb, Dinh, Thanh Cong, Singh, Mandip
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9964872/
https://www.ncbi.nlm.nih.gov/pubmed/36839877
http://dx.doi.org/10.3390/pharmaceutics15020554
_version_ 1784896616431353856
author Kalvala, Anil Kumar
Bagde, Arvind
Arthur, Peggy
Kulkarni, Tanmay
Bhattacharya, Santanu
Surapaneni, Sunil
Patel, Nil Kumar
Nimma, Ramesh
Gebeyehu, Aragaw
Kommineni, Nagavendra
Meckes, Jr., David G.
Sun, Li
Banjara, Bipika
Mosley-Kellum, Keb
Dinh, Thanh Cong
Singh, Mandip
author_facet Kalvala, Anil Kumar
Bagde, Arvind
Arthur, Peggy
Kulkarni, Tanmay
Bhattacharya, Santanu
Surapaneni, Sunil
Patel, Nil Kumar
Nimma, Ramesh
Gebeyehu, Aragaw
Kommineni, Nagavendra
Meckes, Jr., David G.
Sun, Li
Banjara, Bipika
Mosley-Kellum, Keb
Dinh, Thanh Cong
Singh, Mandip
author_sort Kalvala, Anil Kumar
collection PubMed
description In cancer patients, chronic paclitaxel (PTX) treatment causes excruciating pain, limiting its use in cancer chemotherapy. The neuroprotective potential of synthetic cannabidiol (CBD) and CBD formulated in extracellular vesicles (CBD-EVs) isolated from human umbilical cord derived mesenchymal stem cells was investigated in C57BL/6J mice with PTX-induced neuropathic pain (PIPN). The particle size of EVs and CBD-EVs, surface roughness, nanomechanical properties, stability, and release studies were all investigated. To develop neuropathy in mice, PTX (8 mg/kg, i.p.) was administered every other day (four doses). In terms of decreasing mechanical and thermal hypersensitivity, CBD-EVs treatment was superior to EVs treatment or CBD treatment alone (p < 0.001). CBD and CBD-EVs significantly reduced mitochondrial dysfunction in dorsal root ganglions and spinal homogenates of PTX-treated animals by modulating the AMPK pathway (p < 0.001). Studies inhibiting the AMPK and 5HT1A receptors found that CBD did not influence the neurobehavioral or mitochondrial function of PIPN. Based on these results, we hypothesize that CBD and CBD-EVs mitigated PIPN by modulating AMPK and mitochondrial function.
format Online
Article
Text
id pubmed-9964872
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-99648722023-02-26 Cannabidiol-Loaded Extracellular Vesicles from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Paclitaxel-Induced Peripheral Neuropathy Kalvala, Anil Kumar Bagde, Arvind Arthur, Peggy Kulkarni, Tanmay Bhattacharya, Santanu Surapaneni, Sunil Patel, Nil Kumar Nimma, Ramesh Gebeyehu, Aragaw Kommineni, Nagavendra Meckes, Jr., David G. Sun, Li Banjara, Bipika Mosley-Kellum, Keb Dinh, Thanh Cong Singh, Mandip Pharmaceutics Article In cancer patients, chronic paclitaxel (PTX) treatment causes excruciating pain, limiting its use in cancer chemotherapy. The neuroprotective potential of synthetic cannabidiol (CBD) and CBD formulated in extracellular vesicles (CBD-EVs) isolated from human umbilical cord derived mesenchymal stem cells was investigated in C57BL/6J mice with PTX-induced neuropathic pain (PIPN). The particle size of EVs and CBD-EVs, surface roughness, nanomechanical properties, stability, and release studies were all investigated. To develop neuropathy in mice, PTX (8 mg/kg, i.p.) was administered every other day (four doses). In terms of decreasing mechanical and thermal hypersensitivity, CBD-EVs treatment was superior to EVs treatment or CBD treatment alone (p < 0.001). CBD and CBD-EVs significantly reduced mitochondrial dysfunction in dorsal root ganglions and spinal homogenates of PTX-treated animals by modulating the AMPK pathway (p < 0.001). Studies inhibiting the AMPK and 5HT1A receptors found that CBD did not influence the neurobehavioral or mitochondrial function of PIPN. Based on these results, we hypothesize that CBD and CBD-EVs mitigated PIPN by modulating AMPK and mitochondrial function. MDPI 2023-02-07 /pmc/articles/PMC9964872/ /pubmed/36839877 http://dx.doi.org/10.3390/pharmaceutics15020554 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
Kalvala, Anil Kumar
Bagde, Arvind
Arthur, Peggy
Kulkarni, Tanmay
Bhattacharya, Santanu
Surapaneni, Sunil
Patel, Nil Kumar
Nimma, Ramesh
Gebeyehu, Aragaw
Kommineni, Nagavendra
Meckes, Jr., David G.
Sun, Li
Banjara, Bipika
Mosley-Kellum, Keb
Dinh, Thanh Cong
Singh, Mandip
Cannabidiol-Loaded Extracellular Vesicles from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Paclitaxel-Induced Peripheral Neuropathy
title Cannabidiol-Loaded Extracellular Vesicles from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Paclitaxel-Induced Peripheral Neuropathy
title_full Cannabidiol-Loaded Extracellular Vesicles from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Paclitaxel-Induced Peripheral Neuropathy
title_fullStr Cannabidiol-Loaded Extracellular Vesicles from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Paclitaxel-Induced Peripheral Neuropathy
title_full_unstemmed Cannabidiol-Loaded Extracellular Vesicles from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Paclitaxel-Induced Peripheral Neuropathy
title_short Cannabidiol-Loaded Extracellular Vesicles from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Paclitaxel-Induced Peripheral Neuropathy
title_sort cannabidiol-loaded extracellular vesicles from human umbilical cord mesenchymal stem cells alleviate paclitaxel-induced peripheral neuropathy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9964872/
https://www.ncbi.nlm.nih.gov/pubmed/36839877
http://dx.doi.org/10.3390/pharmaceutics15020554
work_keys_str_mv AT kalvalaanilkumar cannabidiolloadedextracellularvesiclesfromhumanumbilicalcordmesenchymalstemcellsalleviatepaclitaxelinducedperipheralneuropathy
AT bagdearvind cannabidiolloadedextracellularvesiclesfromhumanumbilicalcordmesenchymalstemcellsalleviatepaclitaxelinducedperipheralneuropathy
AT arthurpeggy cannabidiolloadedextracellularvesiclesfromhumanumbilicalcordmesenchymalstemcellsalleviatepaclitaxelinducedperipheralneuropathy
AT kulkarnitanmay cannabidiolloadedextracellularvesiclesfromhumanumbilicalcordmesenchymalstemcellsalleviatepaclitaxelinducedperipheralneuropathy
AT bhattacharyasantanu cannabidiolloadedextracellularvesiclesfromhumanumbilicalcordmesenchymalstemcellsalleviatepaclitaxelinducedperipheralneuropathy
AT surapanenisunil cannabidiolloadedextracellularvesiclesfromhumanumbilicalcordmesenchymalstemcellsalleviatepaclitaxelinducedperipheralneuropathy
AT patelnilkumar cannabidiolloadedextracellularvesiclesfromhumanumbilicalcordmesenchymalstemcellsalleviatepaclitaxelinducedperipheralneuropathy
AT nimmaramesh cannabidiolloadedextracellularvesiclesfromhumanumbilicalcordmesenchymalstemcellsalleviatepaclitaxelinducedperipheralneuropathy
AT gebeyehuaragaw cannabidiolloadedextracellularvesiclesfromhumanumbilicalcordmesenchymalstemcellsalleviatepaclitaxelinducedperipheralneuropathy
AT kommineninagavendra cannabidiolloadedextracellularvesiclesfromhumanumbilicalcordmesenchymalstemcellsalleviatepaclitaxelinducedperipheralneuropathy
AT meckesjrdavidg cannabidiolloadedextracellularvesiclesfromhumanumbilicalcordmesenchymalstemcellsalleviatepaclitaxelinducedperipheralneuropathy
AT sunli cannabidiolloadedextracellularvesiclesfromhumanumbilicalcordmesenchymalstemcellsalleviatepaclitaxelinducedperipheralneuropathy
AT banjarabipika cannabidiolloadedextracellularvesiclesfromhumanumbilicalcordmesenchymalstemcellsalleviatepaclitaxelinducedperipheralneuropathy
AT mosleykellumkeb cannabidiolloadedextracellularvesiclesfromhumanumbilicalcordmesenchymalstemcellsalleviatepaclitaxelinducedperipheralneuropathy
AT dinhthanhcong cannabidiolloadedextracellularvesiclesfromhumanumbilicalcordmesenchymalstemcellsalleviatepaclitaxelinducedperipheralneuropathy
AT singhmandip cannabidiolloadedextracellularvesiclesfromhumanumbilicalcordmesenchymalstemcellsalleviatepaclitaxelinducedperipheralneuropathy