Local Delivery of Senolytic Drug Inhibits Intervertebral Disc Degeneration and Restores Intervertebral Disc Structure.


Journal

Advanced healthcare materials
ISSN: 2192-2659
Titre abrégé: Adv Healthc Mater
Pays: Germany
ID NLM: 101581613

Informations de publication

Date de publication:
01 2022
Historique:
revised: 09 10 2021
received: 23 07 2021
pubmed: 27 10 2021
medline: 17 3 2022
entrez: 26 10 2021
Statut: ppublish

Résumé

Intervertebral disc (IVD) degeneration (IVDD) is a leading cause of chronic low back pain. There is a strong clinical demand for more effective treatments for IVDD as conventional treatments provide only symptomatic relief rather than arresting IVDD progression. This study shows that senolytic therapy with local drug delivery can inhibit IVDD and restore IVD integrity. ABT263, a senolytic drug, is loaded in poly(lactic-co-glycolic acid) nanoparticles (PLGA-ABT) and intradiscally administered into injury-induced IVDD rat models. The single intradiscal injection of PLGA-ABT may enable local delivery of the drug to avascular IVD, prevention of potential systemic toxicity caused by systemic administration of senolytic drug, and morbidity caused by repetitive injections of free drug into the IVD. The strategy results in the selective elimination of senescent cells from the degenerative IVD, reduces expressions of pro-inflammatory cytokines and matrix proteases in the IVD, inhibits progression of IVDD, and even restores the IVD structure. This study demonstrates for the first time that local delivery of senolytic drug can effectively treat senescence-associated IVDD. This approach can be extended to treat other types of senescence-associated degenerative diseases.

Identifiants

pubmed: 34699690
doi: 10.1002/adhm.202101483
doi:

Substances chimiques

Pharmaceutical Preparations 0
Senotherapeutics 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2101483

Informations de copyright

© 2021 Wiley-VCH GmbH.

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Auteurs

Songhyun Lim (S)

School of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Republic of Korea.

Seong Bae An (SB)

Department of Neurosurgery, CHA University School of Medicine, CHA Bundang Medical Center, Seongnam-si, Gyeonggi-do, 13496, Republic of Korea.

Mungyo Jung (M)

School of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Republic of Korea.

Hari Prasad Joshi (HP)

Department of Neurosurgery, CHA University School of Medicine, CHA Bundang Medical Center, Seongnam-si, Gyeonggi-do, 13496, Republic of Korea.

Hemant Kumar (H)

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat, 382355, India.

Cheesue Kim (C)

School of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Republic of Korea.

Seuk Young Song (SY)

School of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Republic of Korea.

Ju-Ro Lee (JR)

School of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Republic of Korea.

Mikyung Kang (M)

Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, 08826, Republic of Korea.

Inbo Han (I)

Department of Neurosurgery, CHA University School of Medicine, CHA Bundang Medical Center, Seongnam-si, Gyeonggi-do, 13496, Republic of Korea.

Byung-Soo Kim (BS)

School of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Republic of Korea.
Interdisciplinary Program for Bioengineering, Seoul National University, Seoul, 08826, Republic of Korea.
Institute of Chemical Processes, Institute of Engineering Research, BioMAX, Seoul National University, Seoul, 08826, Republic of Korea.

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