Single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis mansoni
| Autor: | Labiba K. El-Khordagui, Amany Abdel Bary, Riham M. El-Moslemany, Mervat Z. El-Azzouni, Maha M. Eissa, Sara A. Abdel Salam |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Drug Male Combination therapy media_common.quotation_subject Drug Compounding Phosphorylcholine 030106 microbiology Administration Oral Schistosomiasis Drug resistance Pharmacology Nanocapsules Praziquantel lcsh:Infectious and parasitic diseases 03 medical and health sciences Mice Schistosomicides Lipid Nanocapsules Multistage activity parasitic diseases medicine Animals Humans lcsh:RC109-216 Tegumental targeting media_common Miltefosine biology Research Nanocombination Schistosoma mansoni biology.organism_classification medicine.disease Schistosomiasis mansoni Disease Models Animal Drug Combinations 030104 developmental biology Infectious Diseases Parasitology Female Scanning electron microscopy medicine.drug |
| Zdroj: | Parasites & Vectors Parasites & Vectors, Vol 13, Iss 1, Pp 1-12 (2020) |
| Popis: | Background The control of schistosomiasis has been centered to date on a single drug, praziquantel, with shortcomings 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 histopathological 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 invasive and juvenile worms, and amelioration of hepatic granulomas (P ≤ 0.05). In addition, scanning electron microscopy 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 integrating 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 combinatorial therapy for schistosomiasis mansoni. Further studies are needed to document the nanocombination safety and explore its prophylactic activity and potential to hinder the onset of resistance to the drug components. |
| Databáze: | OpenAIRE |
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