Screening for an ivermectin slow-release formulation suitable for malaria vector control

Chaccour, Carlos; Barrio, Ángel Irigoyen; Royo, Ana Gloria Gil; Martínez-Urbistondo, Diego; Slater, Hannah; Hammann, Felix; Pozo, J.L. del

doi:10.1186/s12936-015-0618-2

Cited by 41 publications

(42 citation statements)

References 36 publications

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“…Merely shortening the insect vector’s lifespan is predicted to have a significant impact on malaria transmission, since oocyte maturation is a slow, highly temperature-dependent process that requires almost all of the adult mosquito’s remaining lifetime. Widespread treatment of populations with such endectocides has been proposed as a potential approach in the eradication of malaria [158]. This TCP has been the discussion of a 2016 expert review by the WHO, and several topics are worth underlining.…”

Section: Direct Effect On the Insect Vector (Potential Tcp-6)mentioning

confidence: 99%

New developments in anti-malarial target candidate and product profiles

Burrows

Duparc

Gutteridge

et al. 2017

Malar J

409

480

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A decade of discovery and development of new anti-malarial medicines has led to a renewed focus on malaria elimination and eradication. Changes in the way new anti-malarial drugs are discovered and developed have led to a dramatic increase in the number and diversity of new molecules presently in pre-clinical and early clinical development. The twin challenges faced can be summarized by multi-drug resistant malaria from the Greater Mekong Sub-region, and the need to provide simplified medicines. This review lists changes in anti-malarial target candidate and target product profiles over the last 4 years. As well as new medicines to treat disease and prevent transmission, there has been increased focus on the longer term goal of finding new medicines for chemoprotection, potentially with long-acting molecules, or parenteral formulations. Other gaps in the malaria armamentarium, such as drugs to treat severe malaria and endectocides (that kill mosquitoes which feed on people who have taken the drug), are defined here. Ultimately the elimination of malaria requires medicines that are safe and well-tolerated to be used in vulnerable populations: in pregnancy, especially the first trimester, and in those suffering from malnutrition or co-infection with other pathogens. These updates reflect the maturing of an understanding of the key challenges in producing the next generation of medicines to control, eliminate and ultimately eradicate malaria.

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Section: Direct Effect On the Insect Vector (Potential Tcp-6)mentioning

confidence: 99%

New developments in anti-malarial target candidate and product profiles

Burrows

Duparc

Gutteridge

et al. 2017

Malar J

409

480

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“…A major limitation to MDA approaches for malaria has been the logistic challenges of repeated dosing in resource-constrained locations, and this is a particular challenge with the less than 24-hour half-life of ivermectin. Injectable and implantable solutions have been described to prolong effective drug levels (42). However, cost, sterility requirements, procedural complications, and patient preference suggest that oral therapies will be preferable.…”

Section: Discussionmentioning

confidence: 99%

Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals

et al. 2016

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Efforts at elimination of scourges, such as malaria, are limited by the logistic challenges of reaching large rural populations and ensuring patient adherence to adequate pharmacologic treatment. We have developed an oral, ultra–long-acting capsule that dissolves in the stomach and deploys a star-shaped dosage form that releases drug while assuming a geometry that prevents passage through the pylorus yet allows passage of food, enabling prolonged gastric residence. This gastric-resident, drug delivery dosage form releases small-molecule drugs for days to weeks and potentially longer. Upon dissolution of the macrostructure, the components can safely pass through the gastrointestinal tract. Clinical, radiographic, and endoscopic evaluation of a swine large-animal model that received these dosage forms showed no evidence of gastrointestinal obstruction or mucosal injury. We generated long-acting formulations for controlled release of ivermectin, a drug that targets malaria-transmitting mosquitoes, in the gastric environment and incorporated these into our dosage form, which then delivered a sustained therapeutic dose of ivermectin for up to 14 days in our swine model. Further, by using mathematical models of malaria transmission that incorporate the lethal effect of ivermectin against malaria-transmitting mosquitoes, we demonstrated that this system will boost the efficacy of mass drug administration toward malaria elimination goals. Encapsulated, gastric-resident dosage forms for ultra–long-acting drug delivery have the potential to revolutionize treatment options for malaria and other diseases that affect large populations around the globe for which treatment adherence is essential for efficacy.

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“…Recently, ivermectin was discovered as a potential drug for malaria transmission control (8,19,(40)(41)(42) and it has been investigated due to its insecticidal effects (25)(26)(27)43) and its ability to inhibit Plasmodium sporogony (24). Additionally, ivermectin was tested against Plasmodium berghei liver stages in vitro and in vivo (44); it inhibited the development and replication of the parasite inside human hepatoma cells (Huh7) in vitro with an IC 50 of ϳ2 M (2.1 g/ml).…”

Section: Discussionmentioning

confidence: 99%

Ivermectin Impairs the Development of Sexual and Asexual Stages of Plasmodium falciparumIn Vitro

Carvalho

Sandri

Melo

et al. 2019

Antimicrob Agents Chemother

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Ivermectin is the drug of choice for many parasitic infections, with more than one billion doses being distributed in onchocerciasis programs. The drug has been put into focus recently by the malaria community because of its potential to kill blood-sucking mosquitoes, thereby reducing malaria transmission. However, the activity of ivermectin against the malaria parasite itself has been only partly investigated. This study aimed to investigate the in vitro activity of ivermectin against asexual and sexual stages of Plasmodium falciparum. Both asexual and late-stage gametocytes were incubated with ivermectin and control drugs in vitro. The growthinhibiting effects were assessed for asexual stages of different Plasmodium falciparum laboratory strains and culture-adapted clinical isolates using the histidine-rich protein 2 enzyme-linked immunosorbent assay technique. The effect against stage IV/V gametocytes was evaluated based on ATP quantification. Ivermectin showed activities at nanomolar concentrations against asexual stages (50% inhibitory concentration of ϳ100 nM) and stage IV/V gametocytes (500 nM) of P. falciparum. Stagespecific assays suggested that ivermectin arrests the parasite cycle at the trophozoite stage. Ivermectin might add a feature to its "wonder drug" properties with activity against asexual stages of the malaria parasite Plasmodium falciparum. The observed activities might be difficult to reach with current regimens but will be more relevant with future high-dose regimens under investigation. Further studies should be performed to confirm these results in vitro and in vivo.

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Screening for an ivermectin slow-release formulation suitable for malaria vector control

Cited by 41 publications

References 36 publications

New developments in anti-malarial target candidate and product profiles

New developments in anti-malarial target candidate and product profiles

Oral, ultra–long-lasting drug delivery: Application toward malaria elimination goals

Ivermectin Impairs the Development of Sexual and Asexual Stages of Plasmodium falciparumIn Vitro

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