4 years ago

Selective Release System for Antioxidative and Anti-Inflammatory Activities Using H2O2-Responsive Therapeutic Nanoparticles

Selective Release System for Antioxidative and Anti-Inflammatory Activities Using H2O2-Responsive Therapeutic Nanoparticles
A. Y. Kim, Soo N. Park, Ji H. Ha
We developed nanoparticles that were degraded by H2O2, a reactive oxygen species (ROS), to study a drug delivery system that targets damaged skin cells with oxidative stress and inflammation. In this study, tyrosol-incorporated copolyoxalate (TPOX) was synthesized by using 1,4-cyclohexanedimethanol, 4-(2-hydroxyethyl)phenol (tyrosol), and oxalyl chloride (Mw ∼ 8835 Da). In vitro drug release behavior was assessed by loading nile red, a lipophilic fluorescent material such as quercetin, into the TPOX nanoparticles. The results indicated that the release of TPOX nanopaticles depended on the H2O2 concentration, but was pH-independent. We confirmed that TPOX nanoparticles under oxidative conditions in oxidative- or inflammatory-damaged cells selectively released entrapped nile red through the degradation by H2O2 for contributing to antioxidant and anti-inflammatory effects. For application, we prepared and evaluated the cytoprotective effect of quercetin-loaded TPOX (QTPOX) nanoparticles against oxidative and inflammatory stress. They showed a strong cytoprotective effect against H2O2-induced cell damage in HaCaT and RAW 264.7 cells. Also, QTPOX nanoparticles inhibited the main factors of LPS-induced inflammation, including iNOS, COX-2, IL-1, TNF-α, and NO production. These results suggest that QTPOX as H2O2-responsive therapeutic nanoparticles is highly potent and versatile as drug delivery system through selective and intensive drug release mechanism for the treatment of abnormal and inflammatory skin diseases

Publisher URL: http://dx.doi.org/10.1021/acs.biomac.7b00844

DOI: 10.1021/acs.biomac.7b00844

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