Single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis ma
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RESEARCH
Single oral fixed‑dose praziquantel‑miltefosine nanocombination for effective control of experimental schistosomiasis mansoni Maha M. Eissa1, Mervat Z. El‑Azzouni1, Labiba K. El‑Khordagui2* , Amany Abdel Bary3, Riham M. El‑Moslemany2 and Sara A. Abdel Salam1
Abstract Background: The control of schistosomiasis has been centered to date on a single drug, praziquantel, with short‑ comings including treatment failure, reinfection, and emergence of drug resistance. Drug repurposing, combination therapy or nanotechnology were explored to improve antischistosomal treatment. The aim of the present study was to utilize a novel combination of the three strategies to improve the therapeutic profile of praziquantel. This was based on a fixed-dose nanocombination of praziquantel and miltefosine, an antischistosomal repurposing candidate, co-loaded at reduced doses into lipid nanocapsules, for single dose oral therapy. Methods: Two nanocombinations were prepared to provide 250 mg praziquantel-20 mg miltefosine/kg (higher fixed-dose) or 125 mg praziquantel-10 mg miltefosine/kg (lower fixed-dose), respectively. Their antischistosomal efficacy in comparison with a non-treated control and their praziquantel or miltefosine singly loaded counterparts was assessed in murine schistosomiasis mansoni. A single oral dose of either formulation was administered on the initial day of infection, and on days 21 and 42 post-infection. Scanning electron microscopic, parasitological, and his‑ topathological studies were used for assessment. Preclinical data were subjected to analysis of variance and Tukeyʼs post-hoc test for pairwise comparisons. Results: Lipid nanocapsules (~ 58 nm) showed high entrapment efficiency of both drugs (> 97%). Compared to singly loaded praziquantel-lipid nanocapsules, the higher nanocombination dose showed a significant increase in antischistosomal efficacy in terms of statistically significant decrease in mean worm burden, particularly against inva‑ sive and juvenile worms, and amelioration of hepatic granulomas (P ≤ 0.05). In addition, scanning electron micros‑ copy examination showed extensive dorsal tegumental damage with noticeable deposition of nanostructures. Conclusions: The therapeutic profile of praziquantel could be improved by a novel multiple approach integrat‑ ing drug repurposing, combination therapy and nanotechnology. Multistage activity and amelioration of liver pathology could be achieved by a new praziquantel-miltefosine fixed-dose nanocombination providing 250 mg praziquantel-20 mg miltefosine/kg. To the best of our knowledge, this is the first report of a fixed-dose nano-based
*Correspondence: [email protected]; [email protected] 2 Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt Full list of author information is available at the end of the article © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptatio
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