Drug-Free ROS Sponge Polymeric Microspheres Reduce Tissue Damage from Ischemic and Mechanical Injury.
Drug-Free ROS Sponge Polymeric Microspheres Reduce Tissue Damage from Ischemic and Mechanical Injury.
复制标题
DOI：
10.1021/acsbiomaterials.6b00804
复制
发表时间：
2018-04-09
影响因子：
5.8
通讯作者：
Duvall CL
中科院分区：
文献类型：
--
作者：
O'Grady KP;Kavanaugh TE;Cho H;Ye H;Gupta MK;Madonna MC;Lee J;O'Brien CM;Skala MC;Hasty KA;Duvall CL
研究了聚丙烯硫化氢（PPS）微球（MS）对不同活性氧（ROS）的固有抗氧化功能，并在糖尿病外周动脉疾病（PAD）和机械诱导的创伤后骨关节炎（PTOA）模型中探讨了PPS-MS的治疗效果。PPS-MS（直径~ 1 μm）在体外无细胞和基于细胞的实验中显著清除过氧化氢（H2O2）、次氯酸盐和过氧亚硝酸盐，但不清除超氧化物。在糖尿病性PAD小鼠模型和PTOA小鼠模型中均证实了ROS水平升高（特别是H2O2）， H2O2分别增加了5倍和2倍以上。PPS-MS治疗在功能上改善了后肢缺血的恢复，其基础是脚垫血红蛋白饱和度和灌注增加~ 15-25%，以及近端血管的早期重塑。在PTOA模型中，PPS-MS降低了30%的基质金属蛋白酶（MMP）活性，减轻了由此引起的关节软骨损伤。这些结果表明，在损伤性炎症部位局部递送PPS-MS可改善慢性高血糖患者对缺血性损伤的血管反应，并减少关节损伤后关节软骨的破坏。这些结果促使我们进一步探索PPS作为一种独立的、局部持续的抗氧化治疗，以及作为一种基于微球的、持续的局部药物递送到有ROS损伤风险的炎症组织的材料。
The inherent antioxidant function of poly(propylene sulfide) (PPS) microspheres (MS) was dissected for different reactive oxygen species (ROS), and therapeutic benefits of PPS-MS were explored in models of diabetic peripheral arterial disease (PAD) and mechanically induced post-traumatic osteoarthritis (PTOA). PPS-MS (∼1 μm diameter) significantly scavenged hydrogen peroxide (H2O2), hypochlorite, and peroxynitrite but not superoxide in vitro in cell-free and cell-based assays. Elevated ROS levels (specifically H2O2) were confirmed in both a mouse model of diabetic PAD and in a mouse model of PTOA, with greater than 5- and 2-fold increases in H2O2, respectively. PPS-MS treatment functionally improved recovery from hind limb ischemia based on ∼15–25% increases in hemoglobin saturation and perfusion in the footpads as well as earlier remodeling of vessels in the proximal limb. In the PTOA model, PPS-MS reduced matrix metalloproteinase (MMP) activity by 30% and mitigated the resultant articular cartilage damage. These results suggest that local delivery of PPS-MS at sites of injury-induced inflammation improves the vascular response to ischemic injury in the setting of chronic hyperglycemia and reduces articular cartilage destruction following joint trauma. These results motivate further exploration of PPS as a stand-alone, locally sustained antioxidant therapy and as a material for microsphere-based, sustained local drug delivery to inflamed tissues at risk of ROS damage.
登录
查看更多内容
DOI：
10.1016/j.nano.2015.01.011
发表时间：
2015-05-01
影响因子：
5.4
作者：
Cho, Hongsik;Pinkhassik, Eugene;Hasty, Karen A.
通讯作者：
Hasty, Karen A.
DOI：
10.1016/j.jconrel.2012.07.042
发表时间：
2012-09-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Gupta MK;Meyer TA;Nelson CE;Duvall CL
通讯作者：
Duvall CL
影响因子：
4.8
作者：
Collins, John A.;Wood, Scott T.;Loeser, Richard F.
通讯作者：
Loeser, Richard F.
影响因子：
6
作者：
Ebrahimian, Teni G.;Heymes, Christophe;Silvestre, Jean-Sebastien
通讯作者：
Silvestre, Jean-Sebastien
影响因子：
2.8
作者：
Buckwalter JA;Anderson DD;Brown TD;Tochigi Y;Martin JA
通讯作者：
Martin JA