Local treatment of experimental colitis in the rat by negatively charged liposomes of catalase, TMN and SOD

Abstract

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.

Keywords: :

• Experimental colitis
• DNBS
• local therapy
• charged liposomes
• catalase
• tempamine

Acknowledgements

The results reported here are included in the dissertation projects of Tareq Jubeh in partial fulfillment of his PhD degree requirements and Mirela Nadler-Milbauer in partial fulfillment of her MSc degree requirements at The Hebrew University of Jerusalem. The study was supported in part by the Barenholz Fund. The skilful assistance of Mr Dror Livne and the help of Dr Jackie Kleinstern in editing the manuscript are acknowledged with pleasure. Abraham Rubinstein is affiliated with the David R. Bloom Center of Pharmacy.