Document Detail


The enhancement of immunosuppressive effects of cyclosporine A on human T-cells using fusogenic liposomes.
MedLine Citation:
PMID:  18930640     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aim of this study was to prepare and characterize neutral, positively charged, negatively charged and fusogenic liposomes of different sizes that contain cyclosporine A (CyA) and to evaluate their immunosuppressive activity on human T-cells. Neutral liposomes containing CyA were prepared from dipalmitoylphosphatidylcholine (DPPC) and cholesterol using the solvent evaporation method. To prepare positively charged, negatively charged and fusogenic liposomes containing CyA; stearylamine (SA), dicetylphosphate (DCP) and dioleoylphosphatidylethanolamine (DOPE) were added to the neutral liposome formulation, respectively. To reduce the size of liposomes containing CyA, extrusion through polycarbonate filters (1000, 400 and 100 nm) was used. The liposomes were characterized by their size, zeta potential and encapsulation efficiency. The in vitro immunosuppressive effects of an aqueous solution of CyA and different liposomes containing CyA were determined on human T-cells by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. The mean diameter of the various multilamellar vesicle (MLV) liposomes containing CyA was between 1.76 and 2.49 microm. The encapsulation efficiency for the different MLV and extruded liposomes containing CyA ranged from 73% to 90%. In vitro immunosuppressive evaluation by T-cell culture showed that fusogenic liposomes have the best inhibitory effects on T-cell proliferation compared to the other liposomes. Reducing the size of the liposomes did not affect the in vitro immunosuppressive activity. The average IC(50) for the aqueous solution of CyA and the neutral, positively charged, negatively charged and fusogenic liposomes containing CyA was 4.98 x 10(-2), 7.38, 1.43, 3.84 x 10(-3) and 7.93 x 10(-5) mM, respectively. The results of this study indicate that fusogenic liposomes have the strongest immunosuppressive activity and could be considered as a suitable delivery system for CyA.
Authors:
Bizhan Malaekeh-Nikouei; Mahmoud R Jaafari; Sayyed A Sajadi Tabassi; Afshin Samiei
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-09-10
Journal Detail:
Title:  Colloids and surfaces. B, Biointerfaces     Volume:  67     ISSN:  1873-4367     ISO Abbreviation:  Colloids Surf B Biointerfaces     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-11-10     Completed Date:  2009-04-20     Revised Date:  2009-10-16    
Medline Journal Info:
Nlm Unique ID:  9315133     Medline TA:  Colloids Surf B Biointerfaces     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  238-44     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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MeSH Terms
Descriptor/Qualifier:
Amines / chemistry
Cyclosporine / pharmacology*
Humans
Immunosuppressive Agents / chemistry,  pharmacology*
Liposomes / chemical synthesis,  chemistry,  pharmacology*
Phosphatidylethanolamines / chemistry
Phosphoric Acid Esters / chemistry
T-Lymphocytes / drug effects*
Chemical
Reg. No./Substance:
0/Amines; 0/Immunosuppressive Agents; 0/Liposomes; 0/Phosphatidylethanolamines; 0/Phosphoric Acid Esters; 124-30-1/stearylamine; 2197-63-9/dicetylphosphate; 2462-63-7/dioleoyl phosphatidylethanolamine; 59865-13-3/Cyclosporine

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


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