Abstract
Minocycline has been proposed as a way to blunt neurovascular injury from matrix metalloproteinases (MMPs) during stroke. However, recent clinical trials suggest that high levels of minocycline may have deleterious side-effects. Here, we showed that very high minocycline concentrations damage endothelial cells via calpain/caspase pathways. To alleviate this potential cytotoxicity, we encapsulated minocycline in liposomes. Low concentrations of minocycline could not reduce tumor necrosis factor α (TNFα)-induced MMP-9 release from endothelial cells. But low concentrations of minocycline-loaded liposomes significantly reduced TNFα-induced MMP-9 release. This study provides proof-of-concept that liposomes may be used to deliver lower levels of minocycline for targeting MMPs in cerebral endothelium.
Original language | English (US) |
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Pages (from-to) | 983-988 |
Number of pages | 6 |
Journal | Journal of Cerebral Blood Flow and Metabolism |
Volume | 32 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2012 |
Keywords
- brain endothelial cell
- calpain
- caspase
- cell death
- liposome
- minocycline
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
- Cardiology and Cardiovascular Medicine