Local treatment of experimental colitis in the rat by negatively charged liposomes of catalase, TMN and SOD.
Superoxide dismutase (SOD), 4-amino tempol (tempamine, denoted as TMN) and catalase were encapsulated into negatively charged liposomes. The activity of the antioxidants against dinitrobenzenesulfonic acid (DNBS) induced colitis was tested in the rat and compared to the anti-inflammatory activity of the native enzymes and free TMN. Inflammation severity was assessed by monitoring tissue myeloperoxidase (MPO) activity, thiobarbituric acid reactive species (TBARS) amounts and by comparing the weights of the dissected colons. In all cases, the liposomal preparations of the antioxidants were more effective than the free molecules in the treatment of the experimental colitis, probably due to the attachment of the negatively charged liposomes, and consequently a longer residence time and better uptake of the antioxidants to the inflamed mucosa. This study suggests that low and high molecular weight antioxidants delivered via anionic liposomes can serve as a novel targeted therapy to treat chronic inflammation of the colonic epithelium, such as ulcerative colitis.
Jubeh
Tareq Taha
TT
Faculty of Medicine, School of Pharmacy, The Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91120, Israel.
Nadler-Milbauer
Mirela
M
Barenholz
Yechezkel
Y
Rubinstein
Abraham
A
D000818:Animals; D003092:Colitis / Q000188:drug therapy* / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000737:chemistry / Q000627:therapeutic use*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D003497:Cyclic N-Oxides; D017392:Thiobarbituric Acid Reactive Substances; C015527:4-amino-TEMPO; D009195:Peroxidase; D013482:Superoxide Dismutase