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Glibenclamide Nanocrystal-Loaded Bioactive Polymeric Scaffolds for Skin Regeneration: In Vitro Characterization and Preclinical Evaluation
Pharmaceutics ( IF 5.4 ) Pub Date : 2021-09-14 , DOI: 10.3390/pharmaceutics13091469
Julie R Youssef 1 , Nabila A Boraie 1 , Heba F Ibrahim 2 , Fatma A Ismail 1 , Riham M El-Moslemany 1
Affiliation  

Skin restoration following full-thickness injury poses significant clinical challenges including inflammation and scarring. Medicated scaffolds formulated from natural bioactive polymers present an attractive platform for promoting wound healing. Glibenclamide was formulated in collagen/chitosan composite scaffolds to fulfill this aim. Glibenclamide was forged into nanocrystals with optimized colloidal properties (particle size of 352.2 nm, and polydispersity index of 0.29) using Kolliphor as a stabilizer to allow loading into the hydrophilic polymeric matrix. Scaffolds were prepared by the freeze drying method using different total polymer contents (3–6%) and collagen/chitosan ratios (0.25–2). A total polymer content of 3% at a collagen/chitosan ratio of 2:1 (SCGL3-2) was selected based on the results of in vitro characterization including the swelling index (1095.21), porosity (94.08%), mechanical strength, rate of degradation and in vitro drug release. SCGL3-2 was shown to be hemocompatible based on the results of protein binding, blood clotting and percentage hemolysis assays. In vitro cell culture studies on HSF cells demonstrated the biocompatibility of nanocrystals and SCGL3-2. In vivo studies on a rat model of a full-thickness wound presented rapid closure with enhanced histological and immunohistochemical parameters, revealing the success of the scaffold in reducing inflammation and promoting wound healing without scar formation. Hence, SCGL3-2 could be considered a potential dermal substitute for skin regeneration.

中文翻译:

用于皮肤再生的载有格列本脲纳米晶体的生物活性聚合物支架:体外表征和临床前评估

全层损伤后的皮肤修复带来了重大的临床挑战,包括炎症和疤痕形成。由天然生物活性聚合物配制的药物支架为促进伤口愈合提供了一个有吸引力的平台。格列本脲配制在胶原蛋白/壳聚糖复合支架中以实现这一目标。使用 Kolliphor 作为稳定剂,将格列本脲制成具有优化胶体特性(粒径为 352.2 nm,多分散指数为 0.29)的纳米晶体,以允许加载到亲水性聚合物基质中。使用不同的总聚合物含量 (3–6%) 和胶原蛋白/壳聚糖比率 (0.25–2),通过冷冻干燥法制备支架。在胶原蛋白/壳聚糖比例为 2 时,总聚合物含量为 3%:1(SCGL3-2)是根据溶胀指数(1095.21)、孔隙率(94.08%)、机械强度、降解速率和体外药物释放等体外表征结果选择的。根据蛋白质结合、凝血和溶血百分比测定的结果,SCGL3-2 显示出血液相容性。HSF 细胞的体外细胞培养研究证明了纳米晶体和 SCGL3-2 的生物相容性。对全层伤口大鼠模型的体内研究显示,组织学和免疫组化参数增强,可快速闭合,揭示了支架在减少炎症和促进伤口愈合而不形成疤痕方面的成功。因此,SCGL3-2 可被视为皮肤再生的潜在真皮替代品。降解速率和体外药物释放。根据蛋白质结合、凝血和溶血百分比测定的结果,SCGL3-2 显示出血液相容性。HSF 细胞的体外细胞培养研究证明了纳米晶体和 SCGL3-2 的生物相容性。对全层伤口大鼠模型的体内研究显示,组织学和免疫组化参数增强,可快速闭合,揭示了支架在减少炎症和促进伤口愈合而不形成疤痕方面的成功。因此,SCGL3-2 可被视为皮肤再生的潜在真皮替代品。降解速率和体外药物释放。根据蛋白质结合、凝血和溶血百分比测定的结果,SCGL3-2 显示出血液相容性。HSF 细胞的体外细胞培养研究证明了纳米晶体和 SCGL3-2 的生物相容性。对全层伤口大鼠模型的体内研究显示,组织学和免疫组化参数增强,可快速闭合,揭示了支架在减少炎症和促进伤口愈合而不形成疤痕方面的成功。因此,SCGL3-2 可被视为皮肤再生的潜在真皮替代品。HSF 细胞的体外细胞培养研究证明了纳米晶体和 SCGL3-2 的生物相容性。对全层伤口大鼠模型的体内研究显示,组织学和免疫组化参数增强,可快速闭合,揭示了支架在减少炎症和促进伤口愈合而不形成疤痕方面的成功。因此,SCGL3-2 可被视为皮肤再生的潜在真皮替代品。HSF 细胞的体外细胞培养研究证明了纳米晶体和 SCGL3-2 的生物相容性。对全层伤口大鼠模型的体内研究显示,组织学和免疫组化参数增强,可快速闭合,揭示了支架在减少炎症和促进伤口愈合而不形成疤痕方面的成功。因此,SCGL3-2 可被视为皮肤再生的潜在真皮替代品。
更新日期:2021-09-15
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