Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2487393 | Journal of Pharmaceutical Sciences | 2008 | 17 Pages |
Abstract
It has been shown that degradation of lipid/DNA complexes (lipoplexes) continues in the dried state during storage. The goal of this study was to evaluate the ability of various strategies to minimize the formation of reactive oxygen species (ROS) in lyophilized lipoplexes during storage, including metal removal from reagents, air displacement, and fortification with chelator/antioxidant agents. Formulations containing individual chelator (DTPA) and antioxidants (Lâmethionine or αâtocopherol), or in combination, were subjected to lyophilization. Accelerated storage conditions were investigated and physicoâchemical characteristics and biological activity of samples were monitored at different time intervals. Generation of ROS during storage was determined by adding proxyl fluorescamine to the formulations prior to freezeâdrying. Lipid peroxidation was assessed by monitoring the formation of thiobarbituric reactive substances (TBARS) and lipid hydroperoxides. We also assessed the effect of increased moisture content on the chemical and biological stability of lipoplexes containing additives. Our results show that both ROS and TBARS are generated in lyophilized cakes during storage, and that agents such as DTPA or αâtocopherol are efficient in protecting lipid/DNA complexes against oxidative damage in the dried state. Our experiments also indicate that higher residual moisture has a deleterious effect on the stability of lipid/DNA complexes during storage. © 2008 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 97:5089-5105, 2008
Keywords
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Authors
Marion D.C. Molina, Thomas J. Anchordoquy,