Aguilar-Vázquez Rocío, Romero-Montero Alejandra, Del Prado-Audelo María L, Cariño-Calvo Lizbeth, González-Del Carmen Manuel, Vizcaíno-Dorado Pablo Adrián, Caballero-Florán Isaac Hiram, Peña-Corona Sheila Iraís, Chávez-Corona Juan Isaac, Bernad-Bernad María Josefa, Magaña Jonathan J, Cortés Hernán, Leyva-Gómez Gerardo
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico.
Tecnologico de Monterrey, Escuela de Ingenieria y Ciencias, Campus Ciudad de Mexico, Ciudad de Mexico 14380, Mexico.
Pharmaceutics. 2024 Jul 30;16(8):1012. doi: 10.3390/pharmaceutics16081012.
Delayed wound healing increases the wound's vulnerability to possible infections, which may have lethal outcomes. The treatments available can be effective, but the urgency is not fully encompassed. The drug repositioning strategy proposes effective alternatives for enhancing medical therapies for chronic diseases. Likewise, applying wound dressings as biodegradable membranes is extremely attractive due to their ease of application, therapeutic effectiveness, and feasibility in industrial manufacturing. This article aims to demonstrate the pleiotropic effects during insulin repositioning in wound closure by employing a biopolymeric membrane-type formulation with insulin. We prepared biopolymeric membranes with sodium alginate cross-linked with calcium chloride, supported in a mixture of xanthan gum and guar gum, and plasticized with glycerol and sorbitol. Human insulin was combined with poloxamer 188 as a protein stabilizing agent. Our investigation encompassed physicochemical and mechanical characterization, antioxidant and biological activity through antibacterial tests, cell viability assessments, and scratch assays as an in vitro and in vivo wound model. We demonstrated that our biopolymeric insulin membranes exhibited adequate manipulation and suitable mechanical resistance, transparency, high swelling capability (1100%), and 30% antioxidant activity. Furthermore, they exhibited antibacterial activity (growth inhibition of at 85% and at 75%, respectively), and insulin promoted wound closure in vitro with a 5.5-fold increase and 72% closure at 24 h. Also, insulin promoted in vivo wound closure with a 3.2-fold increase and 92% closure at 10 days compared with the groups without insulin, and this is the first report that demonstrates this therapeutic effect with two administrations of 0.7 IU. In conclusion, we developed a multifunctional insulin-loaded biopolymeric membrane in this study, with the main activity derived from insulin's role in wound closure and antioxidant activity, augmented by the antimicrobial effect attributed to the polymer poloxamer 188. The synergistic combination of excipients enhances its usefulness and highlights our innovation as a promising material in wound healing materials.
伤口愈合延迟会增加伤口感染的可能性，而感染可能会导致致命后果。现有的治疗方法可能有效，但仍未完全解决紧迫性问题。药物重新定位策略为增强慢性病的医学治疗提供了有效的替代方案。同样，将伤口敷料应用为可生物降解的膜极具吸引力，因为它们易于应用、具有治疗效果且在工业制造中具有可行性。本文旨在通过使用含胰岛素的生物聚合物膜型制剂来证明胰岛素重新定位在伤口闭合过程中的多效性作用。我们制备了与氯化钙交联的海藻酸钠生物聚合物膜，该膜以黄原胶和瓜尔胶的混合物为支撑，并以甘油和山梨醇增塑。人胰岛素与泊洛沙姆188作为蛋白质稳定剂结合。我们的研究包括物理化学和机械表征、通过抗菌测试、细胞活力评估以及作为体外和体内伤口模型的划痕试验进行的抗氧化和生物活性研究。我们证明，我们的生物聚合物胰岛素膜表现出良好的可操作性、合适的机械抗性、透明度、高膨胀能力（1100%）和30%的抗氧化活性。此外，它们表现出抗菌活性（分别对[具体细菌1]的生长抑制率为85%，对[具体细菌2]的生长抑制率为75%），并且胰岛素在体外促进伤口闭合，在24小时时增加了5.5倍，闭合率达到72%。此外，与无胰岛素组相比，胰岛素在体内促进伤口闭合，在10天时增加了3.2倍，闭合率达到92%，这是首次报道通过两次0.7 IU给药证明这种治疗效果。总之，我们在本研究中开发了一种多功能载胰岛素生物聚合物膜，其主要活性源自胰岛素在伤口闭合中的作用和抗氧化活性，并因聚合物泊洛沙姆188的抗菌作用而增强。辅料的协同组合提高了其效用，并突出了我们作为伤口愈合材料中一种有前途材料的创新性。
