Miltefosine lipid nanocapsules: Intersection of drug repurposing and nanotechnology for single dose oral treatment of pre-patent schistosomiasis mansoni

El‐Moslemany, Riham M.; Eissa, Maha M.; Ramadan, Alyaa; El-Khordagui, Labiba K.; El‐Azzouni, Mervat Z.

doi:10.1016/j.actatropica.2016.03.038

Cited by 35 publications

(19 citation statements)

References 62 publications

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“…30,47,50,51 For instance, we demonstrated earlier that LNCs significantly enhanced the PD activity of MFS as a potential repurposed antischistosomal agent. 30,50 Efficacy of MFS-LNCs against both mature and prepatent S. mansoni worms in S. mansoni-infected mice in a single oral 20 mg/kg dose was mainly attributed to facilitation of intestinal transport and interaction with the tegument surface, an effect significantly augmented by inclusion of OA as gut membrane permeabilizer 52 and/or fusogenic agent. 43 More recently, MFS was shown to unmask parasite surface antigens not normally exposed to the host during infection, enhancing their serological recognition.…”

Section: Discussionmentioning

confidence: 93%

Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential <em>Schistosoma mansoni</em> tegumental targeting

Amara¹,

Ramadan²,

El‐Moslemany³

et al. 2018

IJN

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PurposeLipid nanocapsules (LNCs) have shown potential to increase the bioavailability and efficacy of orally administered drugs. However, their intestinal translocation to distal target sites and their implication in pharmacokinetic (PK)–pharmacodynamic (PD) relationships are yet to be elucidated. In this study, the effect of LNCs on the PD activity and pharmacokinetics of praziquantel (PZQ), the mainstay of schistosomiasis chemotherapy, was investigated.Materials and methodsThe composition of LNCs was modified to increase PZQ payload and to enhance membrane permeability. PZQ–LNCs were characterized in vitro for colloidal properties, entrapment efficiency (EE%), and drug release. PD activity of the test formulations was assessed in Schistosoma mansoni-infected mice 7 days post-oral administration of a single 250 mg/kg oral dose. Pharmacokinetics of the test formulations and their stability in simulated gastrointestinal (GI) fluids were investigated to substantiate in vivo data.ResultsPZQ–LNCs exhibited good pharmaceutical attributes in terms of size (46–62 nm), polydispersity index (0.01–0.08), EE% (>95%), and sustained release profiles. Results indicated significant efficacy enhancement by reduction in worm burden, amelioration of liver pathology, and extensive damage to the fluke suckers and tegument. This was partly explained by PK data determined in rats. In addition, oral targeting of the worms was supported by the stability of PZQ–LNCs in simulated GI fluids and scanning electron microscopy (SEM) visualization of nanostructures on the tegument of worms recovered from mesenteric/hepatic veins. Cytotoxicity data indicated tolerability of PZQ–LNCs.ConclusionData obtained provide evidence for the ability of oral LNCs to target distal post-absorption sites, leading to enhanced drug efficacy. From a practical standpoint, PZQ–LNCs could be suggested as a potential tolerable single lower dose oral nanomedicine for more effective PZQ mass chemotherapy.

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Section: Discussionmentioning

confidence: 93%

Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential <em>Schistosoma mansoni</em> tegumental targeting

Amara¹,

Ramadan²,

El‐Moslemany³

et al. 2018

IJN

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“…This lead has been further developed using a nanotechnological adjuvant approach based on lipid nanocapsules [76]. The results of this study indicated a strong schistosomicidal effects against both the invasive and the immature stage, further indicated by a significant reduction in worm burdens [76]. …”

Section: Research and Development Of Antischistosomal Drugsmentioning

confidence: 99%

Controlling schistosomiasis with praziquantel: How much longer without a viable alternative?

Bergquist¹,

2017

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The current approach of morbidity control of schistosomiasis, a helminth disease of poverty with considerable public health and socioeconomic impact, is based on preventive chemotherapy with praziquantel. There is a pressing need for new drugs against this disease whose control entirely depends on this single drug that has been widely used over the past 40 years. We argue that a broader anthelminthic approach supplementing praziquantel with new antischistosomals targeting different parasite development stages would not only increase efficacy but also reduce the risk for drug resistance. Repositioning drugs already approved for other diseases provides a shortcut to clinical trials, as it is expected that such drugs rapidly pass the regulatory authorities. The antischistosomal properties of antimalarial drugs (e.g., semisynthetic artemisinins, synthetic trioxolanes, trioxaquines and mefloquine) and of drugs being developed or registered for other purposes (e.g., moxidectin and miltefosin), administered alone or in combination with praziquantel, have been tested in the laboratory and clinical trials. Another avenue to follow is the continued search for new antischistosomal properties in plants. Here, we summarise recent progress made in schistosomiasis chemotherapy, placing particular emphasis on repositioning of existing drugs against schistosomiasis.Electronic supplementary materialThe online version of this article (doi:10.1186/s40249-017-0286-2) contains supplementary material, which is available to authorized users.

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“…Liposome based nanocapsules of praziquantel (PZQ-LNCs) improved the drug efficacy and ameliorated disease pathology [131]. Further, liposomal nanocapsules of miltefosine exerted potential schistosomal effects by ameliorating hepatic histology (reducing the granuloma size, number and inflammation) in single dose [132].…”

Section: Nano-medicinal Approachmentioning

confidence: 99%

Molecular Medicines for Parasitic Diseases

Singh¹

2021

Methods in Molecular Medicine

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Being the cause for significant amount of morbidities and mortalities, parasitic diseases remain the major challenge for the healthcare community due to the limitations associated with the current chemotherapeutics. Drug discovery/invention can be achieved by collaborative efforts of biotechnologists and pharmacists for identifying potential candidates and successfully turn them into medicine for improving the healthcare system. Although molecular medicine for disease intervention is still in its infancy, however, significant research works and successful trials in short span of time have made it broadly accepted among the scientific community. This chapter identifies different molecular medicine approaches for dealing with parasites that have been coming up on the horizon with the new technological advances in bioinformatics and in the field of omics. With the better understanding of the genomics, molecular medicine field has not only raised hopes to deal with parasitic infections but also accelerated the development of personalized medicine. This will provide a targeted approach for identifying the druggable targets and their pathophysiological importance for disease intervention.

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Miltefosine lipid nanocapsules: Intersection of drug repurposing and nanotechnology for single dose oral treatment of pre-patent schistosomiasis mansoni

Cited by 35 publications

References 62 publications

Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential <em>Schistosoma mansoni</em> tegumental targeting

Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential <em>Schistosoma mansoni</em> tegumental targeting

Controlling schistosomiasis with praziquantel: How much longer without a viable alternative?

Molecular Medicines for Parasitic Diseases

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Miltefosine lipid nanocapsules: Intersection of drug repurposing and nanotechnology for single dose oral treatment of pre-patent schistosomiasis mansoni

Cited by 35 publications

References 62 publications

Praziquantel&ndash;lipid nanocapsules: an oral nanotherapeutic with potential <em>Schistosoma mansoni</em> tegumental targeting

Praziquantel&ndash;lipid nanocapsules: an oral nanotherapeutic with potential <em>Schistosoma mansoni</em> tegumental targeting

Controlling schistosomiasis with praziquantel: How much longer without a viable alternative?

Molecular Medicines for Parasitic Diseases

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Product

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Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential <em>Schistosoma mansoni</em> tegumental targeting

Praziquantel–lipid nanocapsules: an oral nanotherapeutic with potential <em>Schistosoma mansoni</em> tegumental targeting