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来自人脐带间充质干细胞的载大麻二酚细胞外囊泡可减轻紫杉醇诱导的周围神经病变。

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

作者信息

Kalvala Anil Kumar, Bagde Arvind, Arthur Peggy, Kulkarni Tanmay, Bhattacharya Santanu, Surapaneni Sunil, Patel Nil Kumar, Nimma Ramesh, Gebeyehu Aragaw, Kommineni Nagavendra, Meckes David G, Sun Li, Banjara Bipika, Mosley-Kellum Keb, Dinh Thanh Cong, Singh Mandip

机构信息

Department of Pharmaceutics, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32301, USA.

Department of Biochemistry and Molecular Biology, Mayo College of Medicine and Science, Jacksonville, FL 32224, USA.

出版信息

Pharmaceutics. 2023 Feb 7;15(2):554. doi: 10.3390/pharmaceutics15020554.

DOI:10.3390/pharmaceutics15020554
PMID:36839877
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9964872/
Abstract

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 ( < 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 ( < 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.

摘要

在癌症患者中，长期使用紫杉醇（PTX）会导致极度疼痛，限制了其在癌症化疗中的应用。在患有PTX诱导的神经性疼痛（PIPN）的C57BL/6J小鼠中，研究了合成大麻二酚（CBD）以及从人脐带间充质干细胞分离的细胞外囊泡中配制的CBD（CBD-EVs）的神经保护潜力。对细胞外囊泡和CBD-EVs的粒径、表面粗糙度、纳米力学性能、稳定性和释放研究均进行了调查。为了使小鼠发生神经病变，每隔一天给予PTX（8mg/kg，腹腔注射）（共四剂）。在减轻机械性和热超敏反应方面，CBD-EVs治疗优于单独的细胞外囊泡治疗或CBD治疗（P<0.001）。CBD和CBD-EVs通过调节AMPK途径，显著降低了PTX处理动物的背根神经节和脊髓匀浆中的线粒体功能障碍（P<0.001）。抑制AMPK和5HT1A受体的研究发现，CBD不影响PIPN的神经行为或线粒体功能。基于这些结果，我们推测CBD和CBD-EVs通过调节AMPK和线粒体功能减轻了PIPN。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/673d/9964872/cc5216d7e2da/pharmaceutics-15-00554-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/673d/9964872/c5c0cf9855ae/pharmaceutics-15-00554-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/673d/9964872/b00728dbe3b2/pharmaceutics-15-00554-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/673d/9964872/d8d6b560d10f/pharmaceutics-15-00554-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/673d/9964872/da8711b3c9bc/pharmaceutics-15-00554-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/673d/9964872/2d3421666398/pharmaceutics-15-00554-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/673d/9964872/c7e9e54d2710/pharmaceutics-15-00554-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/673d/9964872/def5ed95acec/pharmaceutics-15-00554-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/673d/9964872/cc5216d7e2da/pharmaceutics-15-00554-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/673d/9964872/c5c0cf9855ae/pharmaceutics-15-00554-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/673d/9964872/b00728dbe3b2/pharmaceutics-15-00554-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/673d/9964872/d8d6b560d10f/pharmaceutics-15-00554-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/673d/9964872/da8711b3c9bc/pharmaceutics-15-00554-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/673d/9964872/2d3421666398/pharmaceutics-15-00554-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/673d/9964872/c7e9e54d2710/pharmaceutics-15-00554-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/673d/9964872/def5ed95acec/pharmaceutics-15-00554-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/673d/9964872/cc5216d7e2da/pharmaceutics-15-00554-g008.jpg

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