Polymer Fusion Research Center, Department of Polymer-Nano Science and Technology, Chonbuk National University, Jeonju 561-756, Republic of Korea.
Biomaterials. 2011 Apr;32(11):3021-9. doi: 10.1016/j.biomaterials.2010.11.033. Epub 2011 Feb 2.
The large production of reactive oxygen species (ROS) leads to the oxidative stress and the subsequent functional decline of organ systems. p-Hydroxybenzyl alcohol (HBA) is known to play a pivotal protective role against oxidative stress-related diseases. We have developed biodegradable antioxidant copolyoxalate, in which HBA is chemically incorporated into its backbone for the treatment of oxidative stress-related diseases. HBA-incorporated copolyoxalate (HPOX) was designed to possess aromatic peroxalate ester linkages in its backbone and release HBA during its hydrolytic degradation. Peroxalate ester linkages in the backbone reacted with and scavenged hydrogen peroxide, leading the release of HBA in vitro. HBA released from HPOX exerted excellent antioxidant activity, such as inhibition of nitric oxide (NO) production by suppressing iNOS (inducible nitric oxide synthases) expression in lipopolysaccharide (LPS)-activated RAW 264.7 cells. HPOX nanoparticles delivered intranasally significantly reduced pulmonary inflammation and suppressed the iNOS expression. Given their excellent antioxidant and anti-inflammatory activities, we anticipate that HPOX nanoparticles are highly potent for the treatment of oxidative damage-related diseases, such as asthma.
大量活性氧（ROS）的产生会导致氧化应激，从而使器官系统的功能随后下降。已知对羟基苯甲醇（HBA）在对抗与氧化应激相关的疾病方面发挥着关键的保护作用。我们已经开发出可生物降解的抗氧化共缩醛，其中 HBA 被化学掺入其主链中，用于治疗与氧化应激相关的疾病。HBA 掺入的共缩醛（HPOX）被设计为在其主链中具有芳族过氧酯键，并在其水解降解过程中释放 HBA。主链中的过氧酯键与过氧化氢反应并清除它，导致 HBA 在体外释放。从 HPOX 释放的 HBA 发挥了出色的抗氧化活性，例如通过抑制脂多糖（LPS）激活的 RAW 264.7 细胞中的诱导型一氧化氮合酶（iNOS）表达来抑制一氧化氮（NO）的产生。经鼻内递送的 HPOX 纳米颗粒可显著减轻肺部炎症并抑制 iNOS 表达。鉴于其出色的抗氧化和抗炎活性，我们预计 HPOX 纳米颗粒非常适合治疗与氧化损伤相关的疾病，如哮喘。
