(446e) Cytotoxicity of An Antioxidant Polymer, Poly(trolox) and Its in Vitro Protective Effect against An Oxidative Stress Injury

Authors: 
Wattamwar, P. - Presenter, University of Kentucky
Meenach, S. A. - Presenter, University of Kentucky
Anderson, K. W. - Presenter, University of Kentucky
Dziubla, T. D. - Presenter, University of Kentucky


The type and severity of a host cell or tissue response to a degradable material depends on the toxicity of its low molecular weight degradation products and its rate of degradation. Studies have found out that local accumulation of the low molecular weight water-soluble and water-insoluble biodegradation products of the polymers can trigger an inflammatory response from the host cell or tissue.[1, 2] Oxidative stress, where oxidative species are generated in excess to the antioxidant defense mechanism, plays a major role in such biomaterial induced inflammatory response. We had proposed an idea of synthesizing biodegradable polymers having native antioxidant activity, biodegradation of which will result in release of active antioxidants, thereby attenuating the injury caused by oxidative stress and local inflammation.

In this work we polymerized trolox, a synthetic antioxidant, to form poly(trolox ester). Trolox is a water-soluble analogue of Vitamin E which scavenges free radicals and provides protection from mild forms of oxidative stress.[3] Polymers of two different molecular weights were synthesized and characterized. Biocompatibility of poly(trolox ester) was determined by performing cytotoxicity studies of poly(trolox ester) nanoparticles and films using Human Umbilical Vein Endothelial Cells (HUVECs). Toxicity and systemic side-effects of some anticancer drugs like doxorubicin is a result of the drug-induced oxidative stress.[4] Antioxidants like Vitamin E, catechin, fullerenol, etc. are shown to have protective effects by scavenging reactive species.[5] Antioxidant functionality of poly(trolox ester) and its degradation products was studied by determining the extent of suppression of reactive species and protection provided by poly(trolox ester) to the HUVECs against an anticancer drug-induced oxidative stress injury.

References:

[1] W. W. Jiang, S. H. Su, R. C. Eberhart, L. Tang, J Biomed Mater Res A 2007, 82, 492.

[2] L. A. Matheson, J. P. Santerre, R. S. Labow, J Cell Physiol 2004, 199, 8.

[3] H. S. Chow, J. J. Lynch, 3rd, K. Rose, D. W. Choi, Brain Res 1994, 639, 102.

[4] Y. Kalender, M. Yel, S. Kalender, Toxicology 2005, 209, 39.

[5] R. Injac, M. Perse, N. Obermajer, V. Djordjevic-Milic, M. Prijatelj, A. Djordjevic, A. Cerar, B. Strukelj, Biomaterials 2008, 29, 3451.