Delivering minocycline into brain endothelial cells with liposome-based technology

Changhong Xing, Tatyana Levchenko, Shuzhen Guo, Monique Stins, Vladimir P. Torchilin, Eng H. Lo

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)983-988
Number of pages6
JournalJournal of Cerebral Blood Flow and Metabolism
Volume32
Issue number6
DOIs
StatePublished - Jun 1 2012

Keywords

  • brain endothelial cell
  • calpain
  • caspase
  • cell death
  • liposome
  • minocycline

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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