Faculty of Medicine, Ain-Shams University, Ramsis St., Abbassia, Cairo, 11566, Egypt.
Faculty of Science, Cairo University, Cairo, Egypt.
Parasitol Res. 2019 Dec;118(12):3519-3533. doi: 10.1007/s00436-019-06475-8. Epub 2019 Oct 31.
The main objective of this work is preparation of mesoporous silica nanoparticles loaded with praziquantel (PZQ-Si) in order to enhance the therapeutic efficacy of praziquantel (PZQ). Mice were experimentally infected with Schistosoma mansoni and treated 6 weeks post-infection with PZQ in different doses via either oral or intraperitoneal (IP) routes. PZQ in the same doses orally administered to S. mansoni-infected mice was used as a drug control, and infected and non-infected non-treated mice served as positive and negative controls, respectively. PZQ-Si exhibited good physicochemical attributes in terms of small uniform size (105 nm), spherical shape, and PZQ entrapment efficiency (83%). A maximum antischistosomal effect was achieved using orally administered PZQ-Si as reflected by total worm burden, tissue egg count, oogram pattern, and hepatic granuloma count and diameter. The biomarkers related to liver oxidative stress status and immunomodulatory effect (serum TNF-α and IL-10) were significantly improved. Data obtained implied that IP route was less efficacious for the delivery of PZQ-Si. Encapsulation of PZQ permits the reduction of the used therapeutic dose of PZQ. Hepatic DNA fragmentation, measured by comet assay, was significantly improved in infected mice treated with maximum dose of PZQ-Si as compared to positive or PZQ control groups. The results indicate that mesoporous silica NP is a promising safe nanocarrier for PZQ potentiating its antischistosomal, antioxidant, immunomodulatory, and anti-inflammatory action in animal model infected with S. mansoni. From a practical standpoint, PZQ-Si using a lower dose of PZQ could be suggested for effective PZQ antischistosomal mass chemotherapy.
本工作的主要目的是制备载有吡喹酮（PZQ-Si）的介孔硅纳米颗粒，以增强吡喹酮（PZQ）的治疗效果。用曼氏血吸虫感染小鼠，并在感染后 6 周通过口服或腹腔内（IP）途径用不同剂量的 PZQ 进行治疗。将相同剂量的 PZQ 口服给予曼氏血吸虫感染小鼠作为药物对照，感染和未感染未治疗的小鼠分别作为阳性和阴性对照。PZQ-Si 表现出良好的物理化学性质，粒径均匀（105nm）、球形和 PZQ 包封效率（83%）。口服给予 PZQ-Si 可获得最大的抗血吸虫作用，表现为总虫负荷、组织虫卵计数、卵谱模式和肝肉芽肿计数和直径。与肝氧化应激状态和免疫调节作用相关的生物标志物（血清 TNF-α和 IL-10）显著改善。数据表明，IP 途径对 PZQ-Si 的递送效果较差。PZQ 的包封允许减少 PZQ 的治疗剂量。与阳性对照组或 PZQ 对照组相比，用最大剂量的 PZQ-Si 治疗的感染小鼠的肝 DNA 片段化（通过彗星试验测量）显著改善。结果表明，介孔硅 NP 是一种有前途的安全纳米载体，可增强其在感染曼氏血吸虫的动物模型中的抗血吸虫、抗氧化、免疫调节和抗炎作用。从实际角度来看，使用较低剂量 PZQ 的 PZQ-Si 可用于有效进行 PZQ 抗血吸虫大规模化疗。
