scholarly journals A single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis mansoni

2020 ◽  
Author(s):  
Maha Mohamed Eissa ◽  
Mervat El-Azzouni ◽  
Labiba Khalil El-Khordagui ◽  
Amany Abdel Bary ◽  
Riham Mohamed El-Moslemany ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Drug Repurposing ◽  
Effective Control ◽  
Fixed Dose ◽  
Electron Microscopic ◽  
Lipid Nanocapsules ◽  
Schistosomiasis Mansoni ◽  
Scanning Electron Microscopic ◽  
Therapeutic Profile ◽  
Scanning Electron

Abstract 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 nontreated 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, the 21st and 42nd days post infection. Scanning electron microscopic, parasitological and histopathological studies were used for assessment. Preclinical data were subjected to analysis of variance and Tukey 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 dose nanocombination 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 microscopic 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.

scholarly journals A single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis mansoni

2020 ◽  
Author(s):  
Maha Mohamed Eissa ◽  
Mervat El-Azzouni ◽  
Labiba Khalil El-Khordagui ◽  
Amany Abdel Bary ◽  
Riham Mohamed El-Moslemany ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Drug Repurposing ◽  
Effective Control ◽  
Fixed Dose ◽  
Electron Microscopic ◽  
Lipid Nanocapsules ◽  
Schistosomiasis Mansoni ◽  
Scanning Electron Microscopic ◽  
Therapeutic Profile ◽  
Scanning Electron

Abstract 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 nontreated 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, the 21st and 42nd days post infection. Scanning electron microscopic, parasitological and histopathological studies were used for assessment. Preclinical data were subjected to analysis of variance and Tukey 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 dose nanocombination 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 microscopic 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.

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

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Maha M. Eissa ◽  
Mervat Z. El-Azzouni ◽  
Labiba K. El-Khordagui ◽  
Amany Abdel Bary ◽  
Riham M. El-Moslemany ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Drug Repurposing ◽  
Entrapment Efficiency ◽  
Effective Control ◽  
Fixed Dose ◽  
Electron Microscopic ◽  
Lipid Nanocapsules ◽  
Schistosomiasis Mansoni ◽  
Therapeutic Profile ◽  
Scanning Electron

Abstract 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.

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

2020 ◽  
Author(s):  
Maha Mohamed Eissa ◽  
Mervat El-Azzouni ◽  
Labiba Khalil El-Khordagui ◽  
Amany Abdel Bary ◽  
Riham Mohamed El-Moslemany ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Drug Repurposing ◽  
Entrapment Efficiency ◽  
Effective Control ◽  
Fixed Dose ◽  
Electron Microscopic ◽  
Lipid Nanocapsules ◽  
Schistosomiasis Mansoni ◽  
Therapeutic Profile ◽  
Scanning Electron

Abstract 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.

scholarly journals A single oral fixed-dose praziquantel-miltefosine nanocombination for effective control of experimental schistosomiasis mansoni

2020 ◽  
Author(s):  
Maha Mohamed Eissa ◽  
Mervat El-Azzouni ◽  
Labiba Khalil El-Khordagui ◽  
Amany Abdel Bary ◽  
Riham Mohamed El-Moslemany ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Drug Repurposing ◽  
Effective Control ◽  
Fixed Dose ◽  
Electron Microscopic ◽  
Lipid Nanocapsules ◽  
Schistosomiasis Mansoni ◽  
Histopathological Studies ◽  
Therapeutic Profile ◽  
Scanning Electron

Abstract Background: The control of schistosomiasis has been centered to date on a single drug, praziquantel (PZQ), 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 PZQ. This was based on a fixed dose nanocombination of PZQ and miltefosine (MFS), an antischistosomal repurposing candidate, co-loaded at reduced doses into lipid nanocapsules (LNCs), for single dose oral therapy. Methods: Two nanocombinations were prepared to provide 250 mg PZQ-20 mg MFS/kg (higher fixed dose) or 125 mg PZQ-10 mg MFS/kg (lower fixed dose) respectively. Their antischistosomal efficacy in comparison with nontreated control and their PZQ or MFS singly loaded counterparts was assessed in murine schistosomiasis mansoni. A single oral dose of either formulation was administered on the initial day of infection, the 21 st and 42 nd days post infection. Scanning electron microscopic (SEM), parasitological and histopathological studies were used for assessment. Preclinical data were subjected to analysis of variance and Tukey post hoc test for pairwise comparisons. Results: Compared to singly loaded PZQ-LNCs, the higher dose nanocombination showed a significant increase in antischistosomal efficacy in terms of % reduction in worm burden, particularly against invasive and juvenile worms, and amelioration of hepatic granulomas. The efficacy of the higher dose nanocombination was significantly greater than that of its lower dose counterpart. SEM showed extensive dorsal tegumental damage with noticeable deposition of nanostructures. Conclusions: The therapeutic profile of PZQ 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 PZQ-MFS fixed dose nanocombination providing 250 mg PZQ-20 mg MFS/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. Key words: Praziquantel, miltefosine, lipid nanocapsules, Schistosoma mansoni, nanocombination, multistage activity, tegumental targeting, scanning electron microscopy

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

2020 ◽  
Author(s):  
Maha Mohamed Eissa ◽  
Mervat El-Azzouni ◽  
Labiba Khalil El-Khordagui ◽  
Amany Abdel Bary ◽  
Riham Mohamed El-Moslemany ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Combination Therapy ◽  
Schistosoma Mansoni ◽  
Drug Repurposing ◽  
Fixed Dose ◽  
Schistosomiasis Control ◽  
Lipid Nanocapsules ◽  
Therapeutic Profile ◽  
Scanning Electron

Abstract 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]

Scanning Electron Microscopic Study of the Cell Surface

1969 ◽  
Vol 27 ◽  
pp. 36-37 ◽  
Author(s):  
Toichiro Kuwabara
Keyword(s):  
Tissue Fluid ◽  
Biological Application ◽  
Biological Structure ◽  
Electron Microscopic ◽  
Surface Appearance ◽  
Minute Amount ◽  
Scanning Electron Microscopic Study ◽  
Scanning Electron Microscopic ◽  
True Structure ◽  
Scanning Electron

Although scanning electron microscopy has a great potential in biological application, there are certain limitations in visualization of the biological structure. Satisfactory techniques to demonstrate natural surfaces of the tissue and the cell have been reported by several investigators. However, it is commonly found that the surface cell membrane is covered with a minute amount of mucin, secretory substance or tissue fluid as physiological, pathological or artefactual condition. These substances give a false surface appearance, especially when the tissue is fixed with strong fixatives. It seems important to remove these coating substances from the surface of the cell for demonstration of the true structure.

A scanning electron microscopic study on dissolving process of cholesterol gallstones by chenodeoxycholic acid (CDCA)

1978 ◽  
Vol 36 (2) ◽  
pp. 522-523
Author(s):  
T. Kanetaka ◽  
M. Cho ◽  
S. Kawamura ◽  
T. Sado ◽  
K. Hara
Keyword(s):  
Electron Microscope ◽  
Chenodeoxycholic Acid ◽  
Outer Surface ◽  
Electron Microscopic ◽  
Cholesterol Gallstones ◽  
The Core ◽  
Scanning Electron Microscopic Study ◽  
Scanning Electron Microscopic ◽  
Acceleration Voltage ◽  
Scanning Electron

The authors have investigated the dissolution process of human cholesterol gallstones using a scanning electron microscope(SEM). This study was carried out by comparing control gallstones incubated in beagle bile with gallstones obtained from patients who were treated with chenodeoxycholic acid(CDCA).The cholesterol gallstones for this study were obtained from 14 patients. Three control patients were treated without CDCA and eleven patients were treated with CDCA 300-600 mg/day for periods ranging from four to twenty five months. It was confirmed through chemical analysis that these gallstones contained more than 80% cholesterol in both the outer surface and the core.The specimen were obtained from the outer surface and the core of the gallstones. Each specimen was attached to alminum sheet and coated with carbon to 100Å thickness. The SEM observation was made by Hitachi S-550 with 20 kV acceleration voltage and with 60-20, 000X magnification.

A Comparative Study of Fractographic Replicas

1974 ◽  
Vol 32 ◽  
pp. 566-567
Author(s):  
Loren Anderson ◽  
Pat Pizzo ◽  
Glen Haydon
Keyword(s):  
Electron Microscopy ◽  
Electron Microscopic Examination ◽  
Direct Examination ◽  
Electron Microscopic ◽  
Reliable Technique ◽  
Service Failures ◽  
Transmission Electron ◽  
Mode Of Failure ◽  
Scanning Electron Microscopic ◽  
Scanning Electron

Transmission electron microscopy of replicas has long been used to study the fracture surfaces of components which fail in service. Recently, the scanning electron microscope (SEM) has gained popularity because it allows direct examination of the fracture surface. However, the somewhat lower resolution of the SEM coupled with a restriction on the sample size has served to limit the use of this instrument in investigating in-service failures. It is the intent of this paper to show that scanning electron microscopic examination of conventional negative replicas can be a convenient and reliable technique for determining mode of failure.

A Scanning Electron Microscopic Study of the Uriniferous Tubules

1973 ◽  
Vol 31 ◽  
pp. 622-623
Author(s):  
Peter M. Andrews
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Renal Glomerulus ◽  
Electron Microscopic ◽  
Vascular Perfusion ◽  
Scanning Electron Microscopic Study ◽  
Scanning Electron Microscopic ◽  
Collecting Tubules ◽  
Bowman's Capsule ◽  
Scanning Electron

Although there have been a number of recent scanning electron microscopic reports on the renal glomerulus, the advantages of scanning electron microscopy have not yet been applied to a systematic study of the uriniferous tubules. In the present investigation, scanning electron microscopy was used to study the ultrastructural morphology of the proximal, distal, thin loop, and collecting tubules. Material for observation was taken from rat kidneys which were fixed by vascular perfusion, sectioned by either cutting or fracturing technigues, and critically point dried.The brush border characterising proximal tubules is first detected on the luminal surface of Bowman's capsule adjacent to the urinary pole orifice. In this region one frequently finds irregular microvilli characterized by broad and flattened bases with occasional bulbous structures protruding from their surfaces.

Human Stapes Crura: Normal Ultrastructure. Scanning Electron Microscopic Findings

1975 ◽  
Vol 33 ◽  
pp. 528-529
Author(s):  
M.D. Graham
Keyword(s):  
Electron Microscope ◽  
Surgical Treatment ◽  
Scanning Electron Microscope ◽  
Osmic Acid ◽  
Human Cadaver ◽  
Electron Microscopic ◽  
Scanning Electron Microscopic ◽  
Normal Human ◽  
Microscopic Findings ◽  
Scanning Electron

The recent development of the scanning electron microscope has added great impetus to the study of ultrastructural details of normal human ossicles. A thorough description of the ultrastructure of the human ossicles is required in order to determine changes associated with disease processes following medical or surgical treatment.Human stapes crura were obtained at the time of surgery for clinical otosclerosis and from human cadaver material. The specimens to be examined by the scanning electron microscope were fixed immediately in the operating room in a cold phosphate buffered 2% gluteraldehyde solution, washed with Ringers, post fixed in cold 1% osmic acid and dehydrated in graded alcohol. Specimens were transferred from alcohol to a series of increasing concentrations of ethyl alcohol and amyl acetate. The tissue was then critical point dried, secured to aluminum stubs and coated with gold, approximately 150A thick on a rotating stage in a vacuum evaporator. The specimens were then studied with the Kent-Cambridge S4-10 Scanning Electron Microscope at an accelerating voltage of 20KV.

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