Transdermal praziquantel administration attenuates hepatic granulomatosis in mice infected with Schistosoma japonicum

Li-zhi, Wu; Xin-sheng, Zheng; Jiang-shan, Dong; Wang, Yi; Yao, Bao-An

doi:10.1007/s00436-015-4324-3

Cited by 3 publications

(3 citation statements)

References 31 publications

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“…These are likely to cause serious local and systemic pathological effects associated with granuloma formation and fibrosis [53]. The significant reduction in hepatic granuloma size could be attributed to the distribution of PZQ [13,54] and MFS [55,56] to the liver of mice. Hepatic granulomas shrink progressively after PZQ treatment because of schistosome killing and reduction in the number of eggs trapped in the liver, reversing fibrogenesis [57].…”

Section: Discussionmentioning

confidence: 99%

Single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis mansoni

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 99%

Single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis mansoni

et al. 2020

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“…These are likely to cause serious local and systemic pathological effects associated with granuloma formation and brosis [53]. The signi cant reduction in hepatic granuloma size could be attributed to the distribution of PZQ [13,54] and MFS [55,56] to the liver of mice. Hepatic granulomas shrink progressively after PZQ treatment because of schistosome killing and reduction in the number of eggs trapped in the liver, reversing brogenesis [57].…”

Section: Discussionmentioning

confidence: 99%

Single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis mansoni

Eissa

El‐Azzouni

El-Khordagui

et al. 2020

Preprint

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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.

show abstract

“…These are likely to cause serious local and systemic pathological effects associated with granuloma formation and fibrosis (53). The significant reduction in hepatic granuloma size could be attributed to the distribution of PZQ (13,54) and MFS (55,56) to the liver of mice. Hepatic granulomas shrink progressively after PZQ treatment as a result of schistosome killing and reduction in the number of eggs trapped in the liver, reversing fibrogenesis (57).…”

Section: Discussionmentioning

confidence: 99%

A single oral fixed - dose praziquantel-miltefosine nanocombination for effective control of experimental Schistosomiasis mansoni

Eissa

El‐Azzouni

El-Khordagui

et al. 2020

Preprint

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Background: Schistosomiasis control has been centered to date on praziquantel, with shortcomings involving ineffectiveness against immature worms, reinfection and emergence of drug resistance. Strategies based on drug repurposing and/or praziquantel combination therapy proved effective, though with some limitations. Combining such strategies with nanotechnology would further augment therapeutic benefits. Nanocarrier-mediated delivery of multiple drugs in schistosomiasis control has not been documented to date. Our objective was to combine drug repurposing, combinational therapy and nanotechnology for the development of a single oral fixed dose nanocombination to improve praziquantel therapeutic profile. This was based on praziquantel and an antischistosomal repurposing candidate miltefosine, co-loaded into lipid nanocapsules in reduced doses. Methods: Two fixed dose lipid nanocapsule formulations were prepared at two concentration levels of praziquantel and miltefosine. Their antischistosomal activity in comparison with control singly loaded lipoid nanocapsules was assessed in Schistosoma mansoni- infected mice. Single oral dos of 250mg praziquantel-20mg miltefosine/kg and 125mg praziquantel-10mg miltefosine/kg were administered on the initial day of infection, 21st and 42nd days post infection. Scanning electron microscopy, parasitological and histopathological studies were used for assessment. In vivo data were subjected to analysis of variance and post hoc test (Tukey) was used for pairwise comparisons. Results: Lipid nanocapsules showed a mean diameter of 58 nm and high entrapment efficiency of both drugs (>95%). Compared to singly loaded lipid nanocapsules, the larger dose praziquantel-miltefosine nanocombination exerted high antischistosomal efficacy in terms of % reduction of worm burden, particularly when given against invasive and juvenile worms, and amelioration of hepatic granulomas. Scanning electron microscopy revealed extensive tegumental damage with noticeable deposition of nanostructures. Conclusions: A fixed dose praziquantel-miltefosine nanocombination offers great potential as a novel single dose oral antischistosomal therapy offering multistage activity and protection against hepatic pathology. The novel drug repurposing/combination therapy/nanotechnology multiple approach has the potentials of improving the therapeutic profile of praziquantel, achieving radical cure, hindering resistance to the component drugs, and simplifying praziquantel chemotherapy. Key words: Praziquantel, miltefosine, lipid nanocapsules, Schistosoma mansoni, nanocombination, multistage activity, tegumental targeting, scanning electron microscopy. [LE1] [LE1]

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Transdermal praziquantel administration attenuates hepatic granulomatosis in mice infected with Schistosoma japonicum

Cited by 3 publications

References 31 publications

Single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis mansoni

Single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis mansoni

Single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis mansoni

A single oral fixed - dose praziquantel-miltefosine nanocombination for effective control of experimental Schistosomiasis mansoni

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