Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400030, China; Collaborative Innovation Center for Brain Science, Chongqing University, Chongqing, 400030, China.
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400030, China; Collaborative Innovation Center for Brain Science, Chongqing University, Chongqing, 400030, China.
Int J Pharm. 2017 Dec 20;534(1-2):179-189. doi: 10.1016/j.ijpharm.2017.10.010. Epub 2017 Oct 5.
The role of surgery for most patients with spontaneous intracerebral haemorrhage (ICH) remains controversial due to the continuous occurrence of postoperative iron overload induced by low clot clearance rate. In this study, human hair keratose hydrogel (KG) loading with minocycline hydrochloride (MH) were prepared to reduce iron overload for the improvement of the postoperative functional recovery after ICH aspiration surgery. Hemoglobin-induced iron accumulation in rat primary neuronal culture was delayed by the adsorptive capacity of blank KG, while MH-loaded KG displayed a stronger and more thorough cytoprotective effect than blank KG due to the combined effect of absorptive action to iron and sustained release of the iron chelator. Moreover, high iron-chelating efficiency in the hematoma region supplied by MH-loaded KG significantly reduced dose strength of iron chelator. In situ injection of KG with different MH loadings (2, 20, and 200μg) into the hematoma region after aspiration surgery showed a stronger effect on the reduction of ICH-induced iron accumulation, edema, and neurological deficits in rats compared to the postoperative intraperitoneal administration of MH (approximately 15mg). These results suggested that the in situ KG not only could effectively reduce the ICH postoperative iron overload and improve the postoperative functional recovery via the iron adsorption and sustained release of MH, but also has great potential to reduce the systemic adverse effects by decreasing the dose strength of iron chelator.
由于血凝块清除率低导致术后持续发生铁过载，手术在大多数自发性脑出血 (ICH) 患者中的作用仍存在争议。在这项研究中，制备了载盐酸米诺环素 (MH) 的人发角蛋白水凝胶 (KG)，以减少铁过载，从而改善 ICH 抽吸手术后的术后功能恢复。空白 KG 的吸附能力延迟了血红蛋白诱导的大鼠原代神经元培养中铁的积累，而 MH 负载的 KG 由于吸附铁和铁螯合剂持续释放的联合作用，表现出更强、更彻底的细胞保护作用。此外，MH 负载的 KG 在血肿区域提供的高铁螯合效率显著降低了铁螯合剂的剂量强度。抽吸手术后向血肿区域内注射不同 MH 载量（2、20 和 200μg）的 KG 与术后腹腔内给予 MH（约 15mg）相比，对减轻大鼠 ICH 诱导的铁积累、水肿和神经功能缺损的效果更强。这些结果表明，原位 KG 不仅可以通过 MH 的铁吸附和持续释放有效降低 ICH 术后铁过载并改善术后功能恢复，而且还可以通过降低铁螯合剂的剂量强度来降低全身不良反应的风险。
