期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 511, 期 2, 页码 1012-1021出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2016.07.071
关键词
Curcumin release; Poly(beta-amino esters); Nanogels; Seahorse bioscience XF96
资金
- National Center for Research Resources
- National Center for Advancing Translational Sciences, National Institutes of Health [UL1TR000117]
- National Institute of Dental and Craniofacial Research, National Institutes of Health [R43 DE02352301]
- National Cancer Institute [P30 CA177558]
Mitochondria are considered to be the power plants of the cell, but can also initiate and execute cell death, stimulated by oxidative stress (OS). OS induced mitochondria] dysfunction is characterized by a loss in oxygen consumption and reduced ATP production. Curcumin, as a potential therapeutic, has been explored as a candidate for mitochondrial OS suppression, but rapid metabolism and aqueous insolubility has prevented it from being effective. Further, efficient delivery of curcumin via the incorporation into nanocarriers has again been limited due to low drug loading capacities and/or significant burst release, resulting in acute cytotoxicity. Hence, to increase the therapeutic potential and reduce the toxic effects of curcumin, curcumin conjugated poly(beta-amino ester) nanogels (CNGs) were synthesized using Michael addition chemistry. This approach provided easy control over the nanogel size, with CNGs showing a uniform release of active curcumin over 48 h with no burst release. This controlled release system significantly increased the safety limit for curcumin, with a ten fold increase in the cytotoxic threshold, as compared to free curcumin. Further, real-time mitochondrial response analysis with the Seahorse XF96 showed effective and prolonged suppression of H2O2 induced mitochondrial oxidative stress upon pre-treating endothelial cells with CNGs and this potential of nanogels was studied at different pre-treatment times prior to H2O2 exposure. (C) 2016 Elsevier B.V. All rights reserved.
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