Department of Pharmaceutical Technology, Faculty of Pharmacy, Ege University, 35100 Bornova, Izmir, Turkey.
Department of Basic Pharmaceutical Sciences, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey.
Eur J Pharm Biopharm. 2017 Oct;119:17-27. doi: 10.1016/j.ejpb.2017.04.027. Epub 2017 Apr 28.
An alternative formulation for the treatment of diabetic foot wounds that heal slowly is a requirement in pharmaceutical field. The aim of this study was to develop a dermal matrix consisting of skin proteins and lipids with an antioxidant that will enhance healing and balance the oxidative stress in the diabetic wound area due to the high levels of glucose. Thus a novel three dimensional collagen-laminin porous dermal matrix was developed by lyophilization. Resveratrol-loaded hyaluronic acid and dipalmitoylphosphatidylcholine microparticles were combined with this dermal matrix. Characterization, in vitro release, microbiological and in vivo studies were performed. Spherical microparticles were obtained with a high RSV encapsulation efficacy. The microparticles were well dispersed in the dermal matrix from the surface to deeper layers. Collagenase degraded dermal matrix, however the addition of RSV loaded microparticles delayed the degradation time. The release of RSV was sustained and reached 70% after 6h. Histological changes and antioxidant parameters in different treatment groups were investigated in full-thickness excision diabetic rat model. Collagen fibers were intense and improved by the presence of formulation without any signs of inflammation. The highest healing score was obtained with the dermal matrix impregnated with RSV-microparticles with an increased antioxidant activity. Collagen-laminin dermal matrix with RSV microparticles was synergistically effective due to presence of skin components in the formulation and controlled release achieved. This combination is a safe and promising option for the treatment of diabetic wounds requiring long recovery.
一种用于治疗糖尿病足部慢性难愈合伤口的替代疗法在制药领域有一定需求。本研究旨在开发一种包含皮肤蛋白和脂质的真皮基质,其中添加一种抗氧化剂,以促进愈合并平衡因高血糖导致的糖尿病伤口区域的氧化应激。因此,通过冷冻干燥法开发了一种新型的具有三层结构的胶原蛋白-层粘连蛋白多孔真皮基质。将负载白藜芦醇的透明质酸和二棕榈酰磷脂酰胆碱微球与该真皮基质结合。对其进行了表征、体外释放、微生物学和体内研究。获得了包封效率高的球形微球。微球在真皮基质中从表面到深层都能很好地分散。胶原酶降解真皮基质,但负载 RSV 的微球的添加会延迟降解时间。RSV 的释放是持续的,6 小时后达到 70%。在全层切除糖尿病大鼠模型中研究了不同治疗组的组织学变化和抗氧化参数。在没有任何炎症迹象的情况下,存在配方会使胶原纤维变得强烈且得到改善。在负载 RSV 微球的真皮基质中获得了最高的愈合评分,其抗氧化活性增强。由于配方中存在皮肤成分和实现了控释,因此胶原蛋白-层粘连蛋白真皮基质与 RSV 微球具有协同增效作用。这种组合是治疗需要长期恢复的糖尿病伤口的一种安全且有前景的选择。