Ávila-Salas Fabian, Marican Adolfo, Pinochet Soledad, Carreño Gustavo, Valdés Oscar, Venegas Bernardo, Donoso Wendy, Cabrera-Barjas Gustavo, Vijayakumar Sekar, Durán-Lara Esteban F
Centro de Nanotecnología Aplicada, Facultad de Ciencias, Universidad Mayor, Huechuraba 8580000, Región Metropolitana, Chile.
Instituto de Química de Recursos Naturales, Universidad de Talca, Talca 3460000, Maule, Chile.
Pharmaceutics. 2019 Sep 2;11(9):447. doi: 10.3390/pharmaceutics11090447.
This research proposes the rational modeling, synthesis and evaluation of film dressing hydrogels based on polyvinyl alcohol crosslinked with 20 different kinds of dicarboxylic acids. These formulations would allow the sustained release of simultaneous bioactive compounds including allantoin, resveratrol, dexpanthenol and caffeic acid as a multi-target therapy in wound healing. Interaction energy calculations and molecular dynamics simulation studies allowed evaluating the intermolecular affinity of the above bioactive compounds by hydrogels crosslinked with the different dicarboxylic acids. According to the computational results, the hydrogels crosslinked with succinic, aspartic, maleic and malic acids were selected as the best candidates to be synthesized and evaluated experimentally. These four crosslinked hydrogels were prepared and characterized by FTIR, mechanical properties, SEM and equilibrium swelling ratio. The sustained release of the bioactive compounds from the film dressing was investigated in vitro and in vivo. The in vitro results indicate a good release profile for all four analyzed bioactive compounds. More importantly, in vivo experiments suggest that prepared formulations could considerably accelerate the healing rate of artificial wounds in rats. The histological studies show that these formulations help to successfully reconstruct and thicken epidermis during 14 days of wound healing. Moreover, the four film dressings developed and exhibited excellent biocompatibility. In conclusion, the novel film dressings based on hydrogels rationally designed with combinatorial and sustained release therapy could have significant promise as dressing materials for skin wound healing.
本研究提出了基于与20种不同二元羧酸交联的聚乙烯醇的薄膜敷料水凝胶的合理建模、合成及评估。这些配方可实现包括尿囊素、白藜芦醇、泛醇和咖啡酸在内的多种生物活性化合物的持续释放，作为伤口愈合的多靶点治疗方法。相互作用能计算和分子动力学模拟研究有助于评估上述生物活性化合物与不同二元羧酸交联的水凝胶的分子间亲和力。根据计算结果，选择与琥珀酸、天冬氨酸、马来酸和苹果酸交联的水凝胶作为实验合成和评估的最佳候选物。制备了这四种交联水凝胶，并通过傅里叶变换红外光谱（FTIR）、力学性能、扫描电子显微镜（SEM）和平衡溶胀率对其进行了表征。研究了薄膜敷料中生物活性化合物的体外和体内持续释放情况。体外结果表明，所有四种分析的生物活性化合物都具有良好的释放曲线。更重要的是，体内实验表明，所制备的配方可显著加快大鼠人工伤口的愈合速度。组织学研究表明，这些配方有助于在伤口愈合的14天内成功重建和增厚表皮。此外，所开发的四种薄膜敷料表现出优异的生物相容性。总之，基于水凝胶合理设计的具有组合和持续释放疗法的新型薄膜敷料作为皮肤伤口愈合的敷料材料具有巨大的应用前景。
