Department of Parasitology and Mycology, School of Medicine and Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
J Glob Antimicrob Resist. 2020 Mar;20:309-315. doi: 10.1016/j.jgar.2019.08.002. Epub 2019 Aug 9.
The aim of this study was to evaluate the efficacy of pyrimethamine-loaded poloxamer 407 nanomicelles on Plasmodium berghei strain NICD in vivo.
Pyrimethamine-loaded nanomicelles were prepared and their zeta potential, particle size and polydispersity index were measured. For antiplasmodial assessment, 54 mice were randomly divided into six groups. Four groups were infected intraperitoneally with P. berghei, whereas the two remaining groups did not receive the parasite (negative controls). Three of the P. berghei-infected groups received treatment with either pyrimethamine-loaded nanomicelles (2 mg/kg), pyrimethamine (2 mg/kg) or empty nanomicelles (2 mg/kg); the fourth group remained untreated (positive control). The parasitaemia rate, survival rate and histopathological changes in the liver, spleen and kidneys were examined and were compared with the negative and positive control groups.
The mean parasitaemia rate differed significantly between the nanoformulated pyrimethamine group and each of the other groups (P<0.05). Moreover, the survival rate of mice in the nanoformulated pyrimethamine group (7/9; 78%) was significantly higher compared with each of the other groups (P<0.01). The main histopathological changes, including hepatic necrosis in the liver, lymphoid hypoplasia in the spleen, and tubular nephrosis and perivascular and interstitial lymphocytic infiltration in the kidneys, were considerably lower in the nanoformulated pyrimethamine group than in the pyrimethamine and positive control groups.
Pyrimethamine-loaded nanomicelles showed potent antimalarial activity and can be considered as a potential candidate for further examination of their suitability as an antimalarial drug.
本研究旨在评估载嘧啶纳米胶束在体内对尼氏疟原虫 NICD 的疗效。
制备载嘧啶纳米胶束并测量其 Zeta 电位、粒径和多分散指数。为了评估抗疟作用，将 54 只小鼠随机分为六组。四组经腹腔感染伯氏疟原虫，其余两组未感染寄生虫（阴性对照）。四组感染伯氏疟原虫的小鼠中有三组接受载嘧啶纳米胶束（2mg/kg）、嘧啶（2mg/kg）或空纳米胶束（2mg/kg）治疗；第四组未接受治疗（阳性对照）。检查疟原虫血症率、存活率和肝、脾、肾的组织病理学变化，并与阴性和阳性对照组进行比较。
纳米载药嘧啶组与其他各组之间的平均疟原虫血症率差异有统计学意义（P<0.05）。此外，纳米载药嘧啶组小鼠的存活率（7/9；78%）明显高于其他各组（P<0.01）。纳米载药嘧啶组的主要组织病理学变化，包括肝坏死、脾淋巴组织减少、肾小管坏死和血管周围及间质淋巴细胞浸润，明显低于嘧啶组和阳性对照组。
载嘧啶纳米胶束具有较强的抗疟活性，可作为进一步研究其作为抗疟药物适用性的候选药物。
