title: Delivering minocycline into brain endothelial cells with liposome-based technology.
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.
authors.affiliation: Departments of Radiology and Neurology, Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
authors.forename: Changhong
authors.initials: C
authors.lastname: Xing
authors.forename: Tatyana
authors.initials: T
authors.lastname: Levchenko
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Guo
authors.forename: Monique
authors.initials: M
authors.lastname: Stins
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Torchilin
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008081:Liposomes; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008911:Minocycline / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9; D008911:Minocycline