Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz PO Box 7146864685, Iran.
Pharmaceutical Nanotechnology Department, Shiraz University of Medical Sciences, Shiraz PO Box 7146864685, Iran.
ACS Appl Bio Mater. 2023 Nov 20;6(11):4620-4628. doi: 10.1021/acsabm.3c00389. Epub 2023 Oct 30.
Wound healing is one of the major global health concerns in diabetic patients. Simvastatin (SMV) is a poorly soluble oral cholesterol-lowering drug that may aid diabetic wound healing. In the current study, a thixotropic peptide hydrogel of Fmoc-diphenylalanine (FmocFF) containing SMV was designed to accelerate skin wound healing effectively and safely in diabetic mice. FmocFF hydrogels were prepared at various concentrations by using the solvent-triggering technique and characterized by spectroscopic methods such as attenuated total reflection Fourier transform infrared (FT-IR) spectroscopy and fluorimetry. Mechanical behaviors were explored by oscillatory rheology. In model mice, the regenerative potential of the FmocFF-SMV hydrogel was evaluated in terms of wound contraction and closure, tissue regeneration, acute and chronic inflammation, granulation, and re-epithelization. The results showed that FmocFF-SMV hydrogels had an entangled nanofibrous microstructure and shear-thinning characteristics. FmocFF-SMV demonstrated a sustained drug release over 7 days. Compared to the unloaded FmocFF hydrogel, treatment with FmocFF-SMV led to superior diabetic wound recovery and reduced inflammation. Therefore, the utilization of the sustained-release FmocFF-SMV hydrogel formulation could become an attractive choice for topical wound therapy in diabetes patients.
伤口愈合是糖尿病患者主要的全球健康问题之一。辛伐他汀（SMV）是一种水溶性差的口服降胆固醇药物，可能有助于糖尿病伤口愈合。在当前的研究中，设计了一种包含 SMV 的 Fmoc-二苯丙氨酸（FmocFF）的触变肽水凝胶，以有效和安全地加速糖尿病小鼠的皮肤伤口愈合。通过溶剂触发技术制备了不同浓度的 FmocFF 水凝胶，并通过衰减全反射傅里叶变换红外（FT-IR）光谱和荧光光谱等光谱方法进行了表征。通过振荡流变学研究了机械性能。在模型小鼠中，根据伤口收缩和闭合、组织再生、急性和慢性炎症、肉芽形成和再上皮化来评估 FmocFF-SMV 水凝胶的再生潜力。结果表明，FmocFF-SMV 水凝胶具有缠结的纳米纤维微观结构和剪切稀化特性。FmocFF-SMV 表现出超过 7 天的持续药物释放。与未加载的 FmocFF 水凝胶相比，用 FmocFF-SMV 处理导致更好的糖尿病伤口恢复和减少炎症。因此，持续释放 FmocFF-SMV 水凝胶制剂的利用可能成为糖尿病患者局部伤口治疗的一个有吸引力的选择。
