School of Pharmacy and Health Professions, Creighton University, Omaha, Nebraska, 68178, USA.
Department of Neurosurgery, University of Nebraska Medical Center, Omaha, Nebraska, 68198, USA.
AAPS PharmSciTech. 2022 Jul 13;23(6):195. doi: 10.1208/s12249-022-02345-2.
Spinal cord injury (SCI) is characterized by mechanical injury or trauma to the spinal cord. Currently, SCI treatment requires extremely high doses of neuroprotective agents, which in turn, causes several adverse effects. To overcome these limitations, the present study focuses on delivery of a low but effective dose of a naturally occurring antioxidant, α-tocopherol (α-TP). Calcium alginate nanoparticles (CA-NP) and poly D,L-lactic-co-glycolic acid nanoparticles (PLGA-NP) prepared by ionotropic gelation and solvent evaporation technique had particle size of 21.9 ± 11.19 and 152.4 ± 10.6 nm, respectively. Surface morphology, surface charge, as well as particle size distribution of both nanoparticles were evaluated. Entrapment of α-TP into CA-NP and PLGA-NP quantified by UPLC showed entrapment efficiency of 4.00 ± 1.63% and 76.6 ± 11.4%, respectively. In vitro cytotoxicity profiles on human astrocyte-spinal cord (HA-sp) showed that blank CA-NP at high concentrations reduced the cell viability whereas blank PLGA-NP showed relatively safer cytotoxic profiles. In addition, PLGA nanoparticles encapsulated with α-TP (α-TP-PLGA-NP) in comparison to α-TP alone at high concentrations were less toxic. Pretreatment of HA-sp cells with α-TP-PLGA-NP showed two-fold higher anti-oxidative protection as compared to α-TP alone, when oxidative stress was induced by HO. In conclusion, CA-NP were found to be unsuitable for treatment of SCI due to their cytotoxicity. Comparatively, α-TP-PLGA-NP were safer and showed high degree of protection against oxidative stress than α-TP alone.
脊髓损伤(SCI)的特征是脊髓受到机械损伤或创伤。目前,SCI 的治疗需要极高剂量的神经保护剂,这反过来又会引起多种不良反应。为了克服这些局限性,本研究专注于递送低剂量但有效的天然抗氧化剂 α-生育酚(α-TP)。通过离子凝胶和溶剂蒸发技术制备的海藻酸钠纳米粒子(CA-NP)和聚 D,L-乳酸-共-羟基乙酸纳米粒子(PLGA-NP)的粒径分别为 21.9±11.19nm 和 152.4±10.6nm。评估了两种纳米粒子的表面形态、表面电荷和粒径分布。UPLC 定量测定 α-TP 包封入 CA-NP 和 PLGA-NP 的包封效率分别为 4.00±1.63%和 76.6±11.4%。体外细胞毒性研究表明,高浓度的空白 CA-NP 降低了人星形胶质细胞-脊髓(HA-sp)的细胞活力,而空白 PLGA-NP 显示出相对更安全的细胞毒性特征。此外,与高浓度的 α-TP 相比,PLGA 纳米粒子包封的 α-TP(α-TP-PLGA-NP)的毒性较低。与单独的 α-TP 相比,HA-sp 细胞用 α-TP-PLGA-NP 预处理后,当由 HO 诱导氧化应激时,显示出两倍更高的抗氧化保护作用。总之,由于 CA-NP 的细胞毒性,它们不适合用于 SCI 的治疗。相比之下,α-TP-PLGA-NP 比单独的 α-TP 更安全,并且对氧化应激表现出高度的保护作用。