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Alkaline-phosphatase triggered self-assemblies enhances the anti-inflammatory property of methylprednisolone in spinal cord injury
Journal of Applied Biomaterials & Functional Materials ( IF 2.5 ) Pub Date : 2021-02-03 , DOI: 10.1177/2280800020978505
Haotao Yu 1 , Ping Zhang 2 , Wei Zhou 2 , Zhihong Zhong 2 , Dongbin Qu 3
Affiliation  

Methylprednisolone sodium phosphate (MP) is an anti-inflammatory corticosteroid which is used in the treatment of spinal cord injury (SCI), however the overdose of MP has toxic effects Therefore it is prerequisite to develop novel approaches to overcome the side effects of MP and enhance its efficacy. In the present work, we have developed alkaline phosphatase (ALP) trigger self-assembly system of oligopeptides to physically entrap and locally deliver MP. The synthesis of Nap-Phe-Phe-Tyr(H2PO3)-OH (1P) was achieved using solid phase peptide synthesis and was characterized using mass spectroscopy. The 1P is a hydrogelator, which in presence of ALP self-assembles to form the hydrogel. During the self-assembly of 1P, MP was physically entrapped without losing the physical strength of hydrogel as revealed in the rheology study. The consistency of this hydrogel and the structure was characterized using circular dichroism. The MP was released from the hydrogel in a sustain manner and 80% of the drug release was observed at 120 h. The MP + 1P were non-toxic to the cells at lower concentration however toxicity increases with the increase in concentration of MP. Further, the in-vivo administration of MP + 1P significantly reduces the pro-inflammatory cytokines and the histological analysis revealed improvement in the SCI. In conclusion, it could be stated that the synthesis of 1P for the delivery of MP provides the novel opportunity in for the treatment of SCI.



中文翻译:

碱性磷酸酶引发的自组装增强甲基强的松龙在脊髓损伤中的抗炎特性

甲基强的松龙磷酸钠 (MP) 是一种抗炎皮质类固醇,用于治疗脊髓损伤 (SCI),但 MP 过量具有毒性作用,因此开发克服 MP 副作用的新方法和增强其功效。在目前的工作中,我们开发了碱性磷酸酶 (ALP) 触发寡肽的自组装系统,以物理捕获和局部递送 MP。Nap-Phe-Phe-Tyr(H 2 PO 3)-OH (1P) 是使用固相肽合成获得的,并使用质谱法进行表征。1P 是一种水凝胶剂,它在 ALP 的存在下自组装形成水凝胶。如流变学研究所示,在 1P 的自组装过程中,MP 在不损失水凝胶物理强度的情况下被物理捕获。这种水凝胶和结构的一致性使用圆二色性表征。MP 以持续方式从水凝胶中释放,在 120 小时观察到 80% 的药物释放。MP + 1P 在较低浓度下对细胞无毒,但毒性随 MP 浓度的增加而增加。此外,MP + 1P 的体内给药显着降低了促炎细胞因子,组织学分析显示 SCI 有所改善。综上所述,

更新日期:2021-02-04
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