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

Abstract

We developed nanoparticles that were degraded by HO, 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 (M ∼ 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 HO 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 HO 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 HO-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 HO-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.

Inhibition of Inflammation‐Associated Thrombosis with ROS‐Responsive Heparin‐DOCA/PVAX Nanoparticles

“…VA release profile is further investigated to evaluate anti‐inflammatory ability. VA release rate accelerates with increased H 2 O 2 level, but lasts longer span than that of indomethacin (6 vs 2.5 days), confirming the advantage of HDP nanoparticles over conventional drug delivery system in high loading of drug, ROS responsiveness, and long‐term therapy effects …”

“…PVAX was prepared according to method provided by Lee et al Briefly, 1,4‐cyclohexanedimethanol (21.96 mmol) and 4‐hydroxy‐3‐methoxy benzyl alcohol (5.49 mmol) were dissolved in 20 mL of dry tetrahydrofuran (THF) under nitrogen, to which triethylamine (60 mmol) was added dropwise at 4 °C. Oxalyl chloride (27.45 mmol) in 25 mL of dry THF was added to the mixture dropwise at 4 °C.…”

“…Polymer antioxidant, copolyoxalate containing vanillyl alcohol (VA) (PVAX), has been developed recently to reduce the excessive ROS and undesired inflammation. PVAX exhibits high anti‐oxidative capability because of the synergistic effects of H 2 O 2 ‐scavening peroxalate ester bonds and the released VA in the presence of ROS acting as antioxidant . VA is one of the major active components of Gastrodia elata, a herb agent known to have antioxidant and anti‐inflammatory properties.…”

“…PVAX exhibits high anti-oxidative capability because of the synergistic effects of H 2 O 2 -scavening peroxalate ester bonds and the released VA in the presence of ROS acting as antioxidant. [13][14][15] VA is one of the major active components of Gastrodia elata, a herb agent known to have antioxidant and anti-inflammatory properties. Combination of heparin conjugate and PVAX through co-selfassembly provides an efficient way to enhance antioxidant load, prevent premature release of small molecular drug, and further reduce the side effects of heparin.…”

H2O2-Responsive Nanoparticle Based on the Supramolecular Self-Assemble of Cyclodextrin

“…At present, block copolymer approaches for H 2 O 2 -responsive NPs has been widely used and rapidly developed. For instance, a tyrosol incorporated copolyoxalate (TPOX) NPs have been developed by Kim et al (2017) , which demonstrated that TPOX NPs released entrapped nile red through the degradation under H 2 O 2 stimulation and could be used as H 2 O 2 -responsive therapeutic NPs for the treatment and inflammatory. Recently, Gu group have designed a glucose-responsive mechanism directly utilizing H 2 O 2 -sensitive polymeric vesicles by using polyethylene glycol (PEG) and phenylboronic ester (PBE)-conjugated polyserine for smart insulin delivery ( Hu et al, 2017 ).…”