Document Detail


Delivering minocycline into brain endothelial cells with liposome-based technology.
MedLine Citation:
PMID:  22491155     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Changhong Xing; Tatyana Levchenko; Shuzhen Guo; Monique Stins; Vladimir P Torchilin; Eng H Lo
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-04-11
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  32     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-01     Completed Date:  2012-08-03     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  983-8     Citation Subset:  IM    
Affiliation:
Departments of Radiology and Neurology, Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
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MeSH Terms
Descriptor/Qualifier:
Anti-Bacterial Agents / pharmacology*
Brain / cytology,  metabolism*
Cell Line
Endothelial Cells / cytology,  metabolism*
Endothelium, Vascular / cytology,  metabolism*
Humans
Liposomes
Matrix Metalloproteinase 9 / metabolism
Minocycline / pharmacology*
Tumor Necrosis Factor-alpha / metabolism
Grant Support
ID/Acronym/Agency:
ONL001888446//PHS HHS; P01-NS55104/NS/NINDS NIH HHS; R37-NS37074/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Liposomes; 0/Tumor Necrosis Factor-alpha; 10118-90-8/Minocycline; EC 3.4.24.35/Matrix Metalloproteinase 9
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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