Traumatic brain injury (TBI) presents a serious challenge for modern medicine due to the poor regenerative capabilities of the brain, complex pathophysiology, and lack of effective treatment for TBI to date. Tissue-engineered scaffolds have shown some experimental success in vivo; unfortunately, none have yielded consummate results of clinical efficacy. N-acetylcysteine has shown neuroprotective potential. To this end, we developed a N-acetylcysteine (NAC)-loaded poly(lactic-co-glycolic acid) (PLGA) electrospun system for potential neural tissue application for TBI. Scanning electron microscopy showed nanofiber diameters ranging 72–542 nm and 124–592 nm for NAC-free and NAC-loaded PLGA nanofibers, respectively. NAC loading was obtained at 28%, and drug entrapment efficacy was obtained at 84%. A biphasic NAC release pattern that featured an initial burst release (13.9%) stage and a later sustained release stage was noted, thus enabling the prolonged replenishing of NAC and drastically improving cell viability and proliferation. This was evidenced by a significantly higher cell viability and proliferation on NAC-loaded nanofibers for rat pheochromocytoma (PC12) and human glioblastoma multiform (A172) cell lines in comparison to PLGA-only nanofibers. The increased cell viability and cell proliferation on NAC-loaded nanofiber substantiates for the repositioning of NAC as a pharmacological agent in neural tissue regeneration applications.

中文翻译：

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重新定位 N-乙酰半胱氨酸 (NAC)：负载 NAC 的静电纺丝药物输送支架，用于潜在的神经组织工程应用

由于大脑再生能力差、病理生理学复杂以及迄今为止缺乏有效的治疗方法，创伤性脑损伤（TBI）对现代医学提出了严峻的挑战。组织工程支架在体内实验中取得了一些成功；不幸的是，还没有取得临床疗效的完美结果。N-乙酰半胱氨酸显示出神经保护潜力。为此，我们开发了一种负载 N-乙酰半胱氨酸 (NAC) 的聚乳酸-乙醇酸 (PLGA) 电纺系统，用于 TBI 神经组织的潜在应用。扫描电子显微镜显示，不含 NAC 和负载 NAC 的 PLGA 纳米纤维的纳米纤维直径分别为 72-542 nm 和 124-592 nm。NAC 载量为 28%，药物包封率为 84%。注意到一种双相 NAC 释放模式，其特征是最初的突发释放 (13.9%) 阶段和后来的持续释放阶段，从而能够延长 NAC 的补充并大大提高细胞活力和增殖。与仅使用 PLGA 的纳米纤维相比，大鼠嗜铬细胞瘤 (PC12) 和人多形性胶质母细胞瘤 (A172) 细胞系的 NAC 负载纳米纤维的细胞活力和增殖显着提高，证明了这一点。负载 NAC 的纳米纤维上细胞活力和细胞增殖的增加证实了 NAC 作为神经组织再生应用中的药物制剂的重新定位。