Gholami Mobina, Danafer Hossein, Sadeghi Mitra, Daryani Ahmad, Hosseini Seyed Abdollah, Gholami Shirzad
Zanjan Pharmaceutical Nanotechnology Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.
Department of Medicinal Chemistry, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran.
AMB Express. 2025 May 2;15(1):69. doi: 10.1186/s13568-025-01876-8.
The discovery of new drugs with minimal toxicity is crucially important in the search for effective treatments for toxoplasmosis. The study aimed to assess the effectiveness of pyrimethamine-loaded mPEG-PCL copolymeric nanoparticles (mPEG-PCL-Pyr) against Toxoplasma gondii (T. gondii) tachyzoites. The nanoparticles were fabricated using a nano-precipitation method and characterized using DLS and AFM. Through MTT assay, the anti-toxoplasmic activity was gauged. Healthy and infected cell viability, infection index, proliferation index, plaque count, and size were evaluated. Results indicated a maximum drug loading capacity of 11.23% in the nanoparticles. Toxicity testing on Vero cells infected with tachyzoites revealed notable cytotoxic effects at pyrimethamine-equivalent concentrations of 20 and 40 mg/mL in the mPEG-PCL copolymeric nanoparticle formulation. However, as the results indicated, the administration of mPEG-PCL-Pyr resulted in the reduction of intracellular proliferation, infection index, and the number and size of plaques in comparison to uninfected treated cells (P < 0.05). The synthesized Nano drug exhibited slightly better performance than pyrimethamine, despite the lack of statistical significance in the observed distinction (p > 0.05). The study demonstrated that mPEG-PCL copolymeric nanoparticles containing pyrimethamine effectively impede the in vitro replication of T. gondii. The study demonstrated that mPEG-PCL copolymeric nanoparticles containing pyrimethamine effectively impede the in vitro replication of T. gondii. The impact of pyrimethamine resembled that of the synthesized nano-drug on T. gondii tachyzoites, suggesting the potential of these nanoparticles as a promising avenue for toxoplasmosis treatment.
发现毒性极小的新药对于寻找治疗弓形虫病的有效方法至关重要。本研究旨在评估负载乙胺嘧啶的甲氧基聚乙二醇-聚己内酯共聚物纳米颗粒(mPEG-PCL-Pyr)对刚地弓形虫速殖子的有效性。纳米颗粒采用纳米沉淀法制备,并通过动态光散射(DLS)和原子力显微镜(AFM)进行表征。通过MTT法测定抗弓形虫活性。评估健康细胞和感染细胞的活力、感染指数、增殖指数、噬斑计数和大小。结果表明纳米颗粒的最大载药量为11.23%。对感染速殖子的Vero细胞进行毒性测试,结果显示在mPEG-PCL共聚物纳米颗粒制剂中,乙胺嘧啶等效浓度为20和40mg/mL时具有显著的细胞毒性作用。然而,结果表明,与未感染的处理细胞相比,给予mPEG-PCL-Pyr可导致细胞内增殖、感染指数以及噬斑数量和大小的减少(P < 0.05)。尽管观察到的差异缺乏统计学意义(p > 0.05),但合成的纳米药物表现略优于乙胺嘧啶。该研究表明,含乙胺嘧啶的mPEG-PCL共聚物纳米颗粒可有效阻碍刚地弓形虫的体外复制。该研究表明,含乙胺嘧啶的mPEG-PCL共聚物纳米颗粒可有效阻碍刚地弓形虫的体外复制。乙胺嘧啶对刚地弓形虫速殖子的影响与合成纳米药物相似,表明这些纳米颗粒有望成为治疗弓形虫病的有效途径。