Marin Ștefania, Albu Kaya Mădălina Georgiana, Ghica Mihaela Violeta, Dinu-Pîrvu Cristina, Popa Lăcrămioara, Udeanu Denisa Ioana, Mihai Geanina, Enachescu Marius
Department of Collagen, Division Leather and Footwear Research Institute, National Research and Development Institute for Textile and Leather, 031215 Bucharest, Romania.
Center of Surface Science and Nanotechnology, University Politehnica of Bucharest, 060042 Splaiul Independentei 313, Romania.
Pharmaceutics. 2018 Nov 9;10(4):224. doi: 10.3390/pharmaceutics10040224.
The aim of this study is to design, develop and evaluate new biohybrid sponges based on polymers (collagen and polyvinyl alcohol) with and without indomethacin as anti-inflammatory drug model to be used for tissue regeneration in wound healing. Type I fibrillar collagen in the form of a gel and different concentrations of polyvinyl alcohol were mixed together to prepare composite gels. Both control samples, without indomethacin and with indomethacin, were obtained. All samples were crosslinked with glutaraldehyde. By freeze-drying of hydrogels, the spongious forms (matrices) were obtained. The matrices were characterized by FT-IR spectroscopy, scanning electron microscopy (SEM), water absorption, enzymatic degradation and in vitro indomethacin release. The pharmacological effect of the spongious biohybrid matrices was determined on an experimental model of burns induced to Wistar rats. The SEM images showed a porous structure with interconnected pores. Collagen sponges present a structure with pore sizes between 20 and 200 µm, which became more and more compact with polyvinyl alcohol addition. The FT-IR showed interactions between collagen and polyvinyl alcohol. The enzymatic degradation indicated that the most stable matrix is the one with the ratio 75:25 of collagen:polyvinyl alcohol (ACI75), the other ones being degradable in time. The kinetic data of indomethacin release from matrices were fitted with different kinetic models and highlighted a biphasic release of the drug. Such kinetic profiles are targeted in skin wound healing for which important aspects are impaired inflammation and local pain. The treatment with sponges associated with anti-inflammatory drug had beneficial effects on the healing process in experimentally induced burns compared to the corresponding matrices without indomethacin and the classical treated control group.
本研究的目的是设计、开发和评估基于聚合物（胶原蛋白和聚乙烯醇）的新型生物杂交海绵，有无吲哚美辛作为抗炎药物模型，用于伤口愈合中的组织再生。将凝胶形式的I型纤维状胶原蛋白与不同浓度的聚乙烯醇混合在一起制备复合凝胶。获得了不含吲哚美辛和含吲哚美辛的两种对照样品。所有样品均用戊二醛交联。通过水凝胶的冷冻干燥，获得海绵状形式（基质）。通过傅里叶变换红外光谱（FT-IR）、扫描电子显微镜（SEM）、吸水性、酶降解和体外吲哚美辛释放对基质进行表征。在Wistar大鼠烧伤实验模型上测定了海绵状生物杂交基质的药理作用。SEM图像显示具有相互连接孔隙的多孔结构。胶原海绵呈现出孔径在20至200μm之间的结构，随着聚乙烯醇的添加，其结构变得越来越致密。FT-IR显示胶原蛋白和聚乙烯醇之间存在相互作用。酶降解表明，最稳定的基质是胶原蛋白与聚乙烯醇比例为75:25的基质（ACI75），其他基质会随时间降解。吲哚美辛从基质中释放的动力学数据用不同的动力学模型拟合，并突出显示了药物的双相释放。这种动力学曲线适用于皮肤伤口愈合，其中炎症受损和局部疼痛是重要方面。与不含吲哚美辛的相应基质和经典治疗对照组相比，用与抗炎药物相关的海绵进行治疗对实验性诱导烧伤的愈合过程有有益影响。
