Department of Pharmacy, Hebei North University, Hebei Key Laboratory of Neuropharmacology, Zhangjiakou 075000, China.
Life Science Research Center, Hebei North University, Zhangjiakou 075000, China.
Molecules. 2022 Oct 14;27(20):6908. doi: 10.3390/molecules27206908.
Osthol (osthole), known as a neuroprotective drug, has shown potent anticancer activity. However, the potential clinical application of osthol is limited due to its low water solubility and low bioavailability. Polybutyl cyanoacrylate (PBCA) has been widely used to improve the solubility of drugs with poor water solubility. In this study, an orthogonal experimental design (OED) was applied to design the preparation process of PBCA nanoparticles (NPs). Then, nanoparticles were prepared and evaluated in terms of physicochemical properties, in vitro release, and cellular uptake, etc. Further, the anti-cancer activity of osthol-PBCA NPs was demonstrated in SH-SY5Y cells. The pharmacokinetics and area under the curve (AUC) were investigated. The obtained osthol-NPs presented a spherical shape with a particle size of 110 ± 6.7 nm, a polydispersity index (PDI) of 0.126, and a zeta potential of −13 ± 0.32 mV. Compared with the free osthol, the drugs in osthol-NPs presented better stability and sustained release pattern activity. In vitro analysis using SH-SY5Y neuroblastoma cells showed that osthol-loaded nanoparticles displayed a significantly enhanced intracellular absorption process (three times) and cytotoxicity compared with free osthol (p < 0.05, increased 10−20%). The in vivo pharmacokinetic study revealed that the AUC of osthol-NPs was 3.3-fold higher than that of free osthol. In conclusion, osthol-PBCA NPs can enhance the bioactivity of osthol, being proposed as a novel, promising vehicle for drug delivery.
蛇床子素（osthole）作为一种神经保护药物，已显示出强大的抗癌活性。然而，由于其低水溶性和低生物利用度，蛇床子素的潜在临床应用受到限制。聚氰基丙烯酸丁酯（PBCA）已广泛用于提高水溶性差的药物的溶解度。在本研究中，采用正交实验设计（OED）设计了 PBCA 纳米粒（NPs）的制备工艺。然后，从物理化学性质、体外释放、细胞摄取等方面对纳米粒进行了评价。进一步，在 SH-SY5Y 细胞中研究了蛇床子素-PBCA NPs 的抗癌活性。考察了药代动力学和曲线下面积（AUC）。所得蛇床子素-NPs 呈球形，粒径为 110±6.7nm，多分散指数（PDI）为 0.126，zeta 电位为-13±0.32mV。与游离蛇床子素相比，蛇床子素-NPs 中的药物具有更好的稳定性和持续释放模式活性。体外分析用 SH-SY5Y 神经母细胞瘤细胞显示，与游离蛇床子素相比，载药纳米粒显示出明显增强的细胞内吸收过程（三倍）和细胞毒性（p<0.05，增加 10−20%）。体内药代动力学研究表明，蛇床子素-NPs 的 AUC 是游离蛇床子素的 3.3 倍。总之，蛇床子素-PBCA NPs 可以增强蛇床子素的生物活性，有望成为一种新型的药物传递载体。
