Pujari-Palmer Shiuli, Pujari-Palmer Michael, Karlsson Ott Marjam
Department of Medical Sciences, Uppsala University, SE-75185, Uppsala, Sweden.
J Biomed Mater Res B Appl Biomater. 2016 Apr;104(3):568-75. doi: 10.1002/jbm.b.33427. Epub 2015 May 7.
Nanoporous alumina elicits different inflammatory responses dependent on pore size, such as increased complement activation and reactive oxygen species (ROS) production, on 200 versus 20 nm pores. In this study, we attempt to further modulate inflammatory cell response by loading nanoporous alumina membranes (20, 100, and 200 nm pores), with an antioxidant, Trolox, for controlled drug release. For mononuclear cells (MNC) no difference in cell response, due to pore size, was seen when cultured on nonloaded membranes. However, when exposed to membranes loaded with Trolox, 100 uM was enough to quench ROS by more than 95% for all pore sizes. Polymorphonuclear cells (PMNC) produced significantly more ROS when exposed to 20 versus 100 nm pores. For Trolox loaded membranes, this trend reversed, due to slower release of antioxidant from the 20 nm pores. Furthermore, Trolox exhibited a unique effect on PMNCs that has not previously been reported: It delayed the production of ROS in a manner distinct from antioxidant activity. The present study confirms that nanoporous alumina is a suitable vehicle for drug delivery, and that Trolox can successfully modulate the inflammatory response of both MNC and PMNCs.
纳米多孔氧化铝根据孔径大小引发不同的炎症反应，例如在200纳米与20纳米孔径的情况下，补体激活增加以及活性氧（ROS）生成增加。在本研究中，我们尝试通过在纳米多孔氧化铝膜（孔径为20、100和200纳米）上负载抗氧化剂Trolox来进一步调节炎症细胞反应，以实现药物的可控释放。对于单核细胞（MNC），在未负载的膜上培养时，未观察到因孔径大小而导致的细胞反应差异。然而，当暴露于负载有Trolox的膜时，100微摩尔的Trolox足以使所有孔径的ROS淬灭超过95%。多形核细胞（PMNC）在暴露于20纳米孔径与100纳米孔径的膜时产生的ROS显著更多。对于负载有Trolox的膜，由于抗氧化剂从20纳米孔径的膜中释放较慢，这种趋势发生了逆转。此外，Trolox对PMNC表现出一种此前未被报道的独特作用：它以一种不同于抗氧化活性的方式延迟了ROS的产生。本研究证实纳米多孔氧化铝是一种适合药物递送的载体，并且Trolox能够成功调节MNC和PMNC的炎症反应。
