Abstract：
Diabetic wounds present a significant global health challenge exacerbated by chronic hyperglycemia-induced oxidative stress, impeding the natural healing process. Despite various treatment strategies, diabetic foot ulceration lacks standardized therapy. Ferulic acid (FA), known for its potent antidiabetic and antioxidant properties, holds promise for diabetic wound management. However, oral administration of FA faces limitations due to rapid oxidation, stability issues, and low bioavailability. The topical application of FA-loaded chitosan nanoparticles (FA-CSNPs) has emerged as a promising approach to overcome these challenges. Here, we report the development of a sustained-release formulation of FA-CSNPs within a hydrogel matrix composed of Chitosan and gelatin. The FA-CSNPs were synthesized using the ionic gelation method andoptimized through a Central Composite Design (CCD) approach. Characterization of the optimized nanoparticles revealed spherical morphology, a particle size of 56.9 ± 2.5 nm, and an impressive entrapment efficiency of 90.3 ± 2.4 %. Subsequently, an FA-CSNPs-loaded hydrogel was formulated, incorporating chitosan as a gelling agent, gelatin to enhance mechanical properties and cell permeation, and glutaraldehyde as a cross-linker. Comprehensive characterization of the hydrogel included pH, moisture loss, porosity, swelling index, rheology, water vapor transmission rate (WVTR), SEM, TEM, invitro drug release studies, antioxidant activity, antibacterial efficacy, cell cytotoxicity, cell migration studies on L929 fibroblast cell line, and stability studies. The stability study demonstrated negligible variations in particle size, zeta potential, and entrapment efficiency over 60 days, ensuring the stable nature of nanoparticles and hydrogel. This innovative delivery approach embedded within a hydrogel matrix holds significant promise for enhancing the therapeutic efficacy of FA-CSNPs-hydrogel in diabetic wound healing applications.
摘要：
糖尿病伤口是由慢性高血糖引起的氧化应激加剧的全球健康挑战。阻碍自然愈合过程。尽管有各种治疗策略，糖尿病足溃疡缺乏标准化治疗。阿魏酸(FA),以其强大的抗糖尿病和抗氧化特性而闻名，对糖尿病伤口管理有希望。然而,由于快速氧化，口服FA面临限制，稳定性问题,和低生物利用度。负载FA的壳聚糖纳米颗粒（FA-CSNP）的局部应用已成为克服这些挑战的有希望的方法。这里,我们报道了由壳聚糖和明胶组成的水凝胶基质中FA-CSNP的缓释制剂的开发。FA-CSNP是使用离子凝胶法合成的，并通过中央复合设计（CCD）方法进行了优化。优化的纳米粒子的表征显示球形形态，粒径为56.9±2.5nm，和令人印象深刻的捕获效率为90.3±2.4%。随后，配制了加载FA-CSNP的水凝胶，掺入壳聚糖作为胶凝剂，明胶，以提高机械性能和细胞渗透，和戊二醛作为交联剂。水凝胶的综合表征包括pH，水分损失,孔隙度,肿胀指数,流变学,水蒸气透过率（WVTR），SEM,TEM,体外药物释放研究，抗氧化活性，抗菌功效，细胞毒性，L929成纤维细胞系的细胞迁移研究，和稳定性研究。稳定性研究表明，颗粒大小的变化可以忽略不计，zeta电位,和超过60天的诱捕效率，确保纳米粒子和水凝胶的稳定性质。这种嵌入水凝胶基质内的创新递送方法对于增强FA-CSNP-水凝胶在糖尿病伤口愈合应用中的治疗功效具有重要的前景。
