Dealing with schistosomiasis: Current drug discovery strategies

Gemma, Sandra; Federico, Stefano; Brogi, Simone; Brindisi, Margherita; Butini, Stefania; Campiani, Giuseppe

doi:10.1016/bs.armc.2019.06.002

Cited by 11 publications

(12 citation statements)

References 125 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This paper presents a new efficient delivery method of artemisone for treating schistosomiasis in a mouse model. A SMEEDS was developed successfully with the following characteristics: (1) high drug load, (2) simple manufacturing process without special equipment, (3) high storage stability and (4) profound efficacy of oral administration of the dissolved drug, allowing administration of only one-tenth of the dose previously administered in suspensions used for the treatment of schistosomiasis [ 4 ]. The artemisone-loaded SMEDDS system, which was delivered to mice by gavage at an early stage of the infection before the worms reach adulthood, completely eliminated or killed the worms and prevented egg production, the main cause of pathology due to deleterious immune response to egg antigens [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is the first-line treatment, but unfortunately, it is also potent only against the late developing stages of the worm [ 3 ]. Moreover, recently there are increasing numbers of reports indicating non-successful praziquantel treatment because of induction of resistance [ 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…These polymers often undergo autocatalytic degradation, which leads to the formation of acidic microenvironments, complex and nonlinear release profiles and potential degradation of the drug prior to its release. Recently, new polymeric systems have been developed, which, after subcutaneous injection, released artemisone slowly and eliminated most of the schistosomes [4]. The advantage of parenteral administration is the avoidance of the intestinal absorption process.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Oral Administration of Artemisone for the Treatment of Schistosomiasis: Formulation Challenges and In Vivo Efficacy

et al. 2020

View full text Add to dashboard Cite

Artemisone is an innovative artemisinin derivative with applications in the treatment of malaria, schistosomiasis and other diseases. However, its low aqueous solubility and tendency to degrade after solubilisation limits the translation of this drug into clinical practice. We developed a self-microemulsifying drug delivery system (SMEDDS), which is easy to produce (simple mixing) with a high drug load. In addition to known pharmaceutical excipients (Capmul MCM, Kolliphor HS15, propylene glycol), we identified Polysorb ID 46 as a beneficial new additional excipient. The physicochemical properties were characterized by dynamic light scattering, conductivity measurements, rheology and electron microscopy. High storage stability, even at 30 °C, was achieved. The orally administrated artemisone SMEDDS formulation was highly active in vivo in S. mansoni infected mice. Thorough elimination of the adult worms, their eggs and prevention of the deleterious granuloma formation in the livers of infected mice was observed even at a relatively low dose of the drug. The new formulation has a high potential to accelerate the clinical use of artemisone in schistosomiasis and malaria.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Oral Administration of Artemisone for the Treatment of Schistosomiasis: Formulation Challenges and In Vivo Efficacy

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Nevertheless, it is reported that they have also a lot of different and important biological activities [ 16 , 17 ]. Indeed, they are antimicrobials, particularly active in schistosomiasis and malaria [ 18 , 19 , 20 ], anti-inflammatory, antiplatelet, and antiviral agents [ 21 , 22 ], and allosteric modulators of the cannabinoid CB1 receptor [ 23 ], VLA-4 integrin antagonists [ 24 ], and EGFR inhibitors [ 25 ]. Taking into account the multiple factors involved in the pathogenesis of COVID-19, all the activities of diarylureas make them promising tools for the treatment of this disease.…”

Section: Introductionmentioning

confidence: 99%

Diarylureas: Repositioning from Antitumor to Antimicrobials or Multi-Target Agents against New Pandemics

et al. 2021

View full text Add to dashboard Cite

Antimicrobials have allowed medical advancements over several decades. However, the continuous emergence of antimicrobial resistance restricts efficacy in treating infectious diseases. In this context, the drug repositioning of already known biological active compounds to antimicrobials could represent a useful strategy. In 2002 and 2003, the SARS-CoV pandemic immobilized the Far East regions. However, the drug discovery attempts to study the virus have stopped after the crisis declined. Today’s COVID-19 pandemic could probably have been avoided if those efforts against SARS-CoV had continued. Recently, a new coronavirus variant was identified in the UK. Because of this, the search for safe and potent antimicrobials and antivirals is urgent. Apart from antiviral treatment for severe cases of COVID-19, many patients with mild disease without pneumonia or moderate disease with pneumonia have received different classes of antibiotics. Diarylureas are tyrosine kinase inhibitors well known in the art as anticancer agents, which might be useful tools for a reposition as antimicrobials. The first to come onto the market as anticancer was sorafenib, followed by some other active molecules. For this interesting class of organic compounds antimicrobial, antiviral, antithrombotic, antimalarial, and anti-inflammatory properties have been reported in the literature. These numerous properties make these compounds interesting for a new possible pandemic considering that, as well as for other viral infections also for CoVID-19, a multitarget therapeutic strategy could be favorable. This review is meant to be an overview on diarylureas, focusing on their biological activities, not dwelling on the already known antitumor activity. Quite a lot of papers present in the literature underline and highlight the importance of these molecules as versatile scaffolds for the development of new and promising antimicrobials and multitarget agents against new pandemic events.

show abstract

“…A quimioterapia atual e a prevenção da esquistossomose dependem de um único medicamento, o praziquantel (PZQ), enquanto a oxamniquina é um pró-fármaco usado apenas em casos de falha da terapia com PZQ. Nesse cenário, o surgimento de resistência é uma ameaça alarmante (Gemma et al, 2019). Os pacientes são acompanhados mensal ou bimestralmente, onde são realizados exames laboratoriais para a verificação de presença do parasita (Lindholz, 2019).…”

Section: Introductionunclassified

Esquistossomose mansônica: uma análise de indicadores epidemiológicos no Município de Bacuri, Maranhão, Brasil

Filho

Neto

Azevedo

et al. 2020

RSD

View full text Add to dashboard Cite

Objetivo: descrever os principais indicadores epidemiológicos para Esquistossomose mansoni (EM) no município de Bacuri, Maranhão, Brasil. Metodologia: Para isso, realizou-se uma pesquisa documental e quantitativa destes indicadores da EM no município escolhido. O recorte temporal escolhido para a pesquisa foi de 2007 a 2016. Os dados utilizados foram coletados do Programa de Controle da Esquistossomose (PCE) que está contido na seção de Informações de Saúde do Tabulador Genérico de Domínio Público (TABNET) do Departamento de Informática do Sistema Único de Saúde (DATASUS). Resultados e Discussão: Verificou-se que o ano de 2007 apresentou o maior número de pessoas com suspeita de infecção por Schistosoma (n= 8123). Quanto à realização de exames para os casos suspeitos de infecção por Schistosoma mansoni, os anos de 2017 (n= 7237), 2009 (n= 4805), 2010 (n= 4789) e 2014 (n= 6443) foram os que apresentaram maior quantidade. Em 2007 foram registrados 1166 (16,10%) casos positivos, seguido de 2009 com 1122 (23,30%) e 2014 com 901 (13,90%). A baixa carga parasitária (1 a 4 ovos) representou 68% (n= 3.947) da totalidade dos casos, sendo que houve uma cobertura de tratamento para esses indivíduos superior a 95%. Conclusão: Mediante os resultados obtidos, é válido ressaltar que a Esquistossomose mansoni ainda possui foco endêmico em municípios afastados dos centros urbanos, como a cidade avaliada neste trabalho. Dessa forma, tornam-se necessárias condutas do poder público que visem à redução desses casos.

show abstract

Dealing with schistosomiasis: Current drug discovery strategies

Cited by 11 publications

References 125 publications

Oral Administration of Artemisone for the Treatment of Schistosomiasis: Formulation Challenges and In Vivo Efficacy

Oral Administration of Artemisone for the Treatment of Schistosomiasis: Formulation Challenges and In Vivo Efficacy

Diarylureas: Repositioning from Antitumor to Antimicrobials or Multi-Target Agents against New Pandemics

Esquistossomose mansônica: uma análise de indicadores epidemiológicos no Município de Bacuri, Maranhão, Brasil

Contact Info

Product

Resources

About