An overview of Chagas disease treatment

Jannin, J.; Villa, Luís

doi:10.1590/s0074-02762007005000106

Cited by 108 publications

(87 citation statements)

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“…However, despite being effective in treating the acute phase of the infection, these drugs display limited efficacy in the chronic phase of the disease and are associated with several side-effects, including hypersensitivity, dermatitis with cutaneous eruptions, depression of bone marrow and polyneuropathy (Jannin, Villa, 2007;Coura, De Castro, 2002). Therefore, it is urgent to discover new drugs to treat Chagas disease that are highly efficacious in both the acute and chronic phases and are devoid of side-effects (Saraiva et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Preparation, characterization and evaluation of the in vivo trypanocidal activity of ursolic acid-loaded solid dispersion with poloxamer 407 and sodium caprate

Eloy

Saraiva

Albuquerque

et al. 2015

Braz. J. Pharm. Sci.

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Ursolic acid is a promising candidate for treatment of Chagas disease; however it has low aqueous solubility and intestinal absorption, which are both limiting factors for bioavailability. Among the strategies to enhance the solubility and dissolution of lipophilic drugs, solid dispersions are growing in popularity. In this study, we employed a mixture of the surfactants poloxamer 407 with sodium caprate to produce a solid dispersion containing ursolic acid aimed at enhancing both drug dissolution and in vivo trypanocidal activity. Compared to the physical mixture, the solid dispersion presented higher bulk density and smaller particle size. Fourier Transform Infrared Spectroscopy results showed hydrogen bonding intermolecular interactions between drug and poloxamer 407. X-ray diffractometry experiments revealed the conversion of the drug from its crystalline form to a more soluble amorphous structure. Consequently, the solubility of ursolic acid in the solid dispersion was increased and the drug dissolved in a fast and complete manner. Taken together with the oral absorption-enhancing property of sodium caprate, these results explained the increase of the in vivo trypanocidal activity of ursolic acid in solid dispersion, which also proved to be safe by cytotoxicity evaluation using the LLC-MK2 cell line. O ácido ursólico é um candidato promissor para o tratamento da doença de Chagas, contudo este fármaco possui baixa solubilidade aquosa e limitada absorção intestinal, ambos os fatores limitantes da biodisponibilidade. Entre as estratégias para potencializar a solubilidade e a dissolução de fármacos lipofílicos, as dispersões sólidas estão crescendo em popularidade. Neste estudo, empregamos mistura dos tensoativos, poloxamer 407 e caprato de sódio, para produzir dispersão sólida contendo ácido ursólico, com o objetivo de aumentar tanto a dissolução do fármaco quanto a atividade tripanocida in vivo. Comparada à mistura física, a dispersão sólida apresentou maior densidade e menor tamanho de partícula. Os resultados da análise de espectroscopia no infravermelho com transformada de Fourier mostraram interações intermoleculares do tipo ligações de hidrogênio entre o fármaco e o poloxamer 407. Os experimentos de difratometria de raio-X revelaram a conversão do fármaco de sua forma cristalina para a forma amorfa, mais solúvel. Consequentemente, a solubilidade do ácido ursólico em dispersão sólida foi aumentada e o fármaco dissolveu-se de maneira mais rápida e completa. Em conjunto com as propriedades promotoras de absorção oral do caprato de sódio, estes resultados explicaram o aumento da atividade tripanocida in vivo do ácido ursólico em dispersão sólida, que também se provou segura após avaliação de citotoxicidade empregando a linhagem celular LLC-MK2.Unitermos: Ácido ursólico/atividade tripanocida. Doença de Chagas/tratamento. Tensoativos. Dispersões sólidas/dissolução. Poloxamer 407. Caproato de sódio.

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Section: Introductionmentioning

confidence: 99%

Preparation, characterization and evaluation of the in vivo trypanocidal activity of ursolic acid-loaded solid dispersion with poloxamer 407 and sodium caprate

Eloy

Saraiva

Albuquerque

et al. 2015

Braz. J. Pharm. Sci.

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“…In particular, the Southern Cone initiative has successfully interrupted reservoirto-human and human-to-human propagation of the disease in Uruguay, Chile and Brazil in recent years and has led to a marked reduction of the overall prevalence and the population at risk (Dias et al 2002, Schofield et al 2006. However, many challenges remain before full control or elimination of the disease can be achieved among them, inequality of the control programs in the various endemic areas (Attaran 2006, Schofield et al 2006, Aguilar et al 2007, Guhl 2007, limitations of currently available specific chemotherapy, and insufficient treatment coverage for those currently infected with the aetiological agent, the parasitic protozoan Trypanosoma cruzi (Urbina & Docampo 2003, Pinto Dias 2006, Jannin & Villa 2007, Tarleton et al 2007, Rassi et al 2009). …”

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confidence: 99%

Ergosterol biosynthesis and drug development for Chagas disease

Urbina

2009

Mem. Inst. Oswaldo Cruz

188

153

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“…In addition, despite fruitful attempts to control vectorial and blood transmission, Chagas disease still lacks prophylactic therapies and effective chemotherapeutic schemes (Rodrigues Coura & De Castro 2002, Dias 2007. Nifurtimox and benznidazole are used for the treatment of Chagas disease (Urbina 2002); although they are effective for the treatment of acute infections, they present moderate activity, exhibit undesirable side effects and require long dosing schedules for chronic infections, which frequently necessitate the cessation of treatment (Jannin & Villa 2007). In addition, the pharmaceutical industries have given little attention to the design and development of new antiparasitic compounds aromatic dicationic compounds represent a class of DNA minor-groove binding ligands that exhibit high activity against a variety of pathogens, such as bacteria, fungi and protozoa (Werbovetz 2006, Wilson et al 2008.…”

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confidence: 99%

The biological in vitro effect and selectivity of aromatic dicationic compounds on Trypanosoma cruzi

Silva

Batista

et al. 2010

Mem. Inst. Oswaldo Cruz

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Trypanosoma cruzi is a parasite that causes Chagas disease, which affects millions of individuals in endemic areas of Latin America. One hundred years after the discovery of Chagas disease, it is still considered a neglected illness because the available drugs are unsatisfactory. Aromatic compounds represent an important class of DNA minor groove-binding ligands that exhibit potent antimicrobial activity. This study focused on the in vitro activity of 10 aromatic dicationic compounds against bloodstream trypomastigotes and intracellular forms of T. cruzi. Our data demonstrated that these compounds display trypanocidal effects against both forms of the parasite and that seven out of the 10 compounds presented higher anti-parasitic activity against intracellular parasites compared with the bloodstream forms. Additional assays to determine the potential toxicity to mammalian cells showed that the majority of the dicationic compounds did not considerably decrease cellular viability. Fluorescent microscopy analysis demonstrated that although all compounds were localised to a greater extent within the kinetoplast than the nucleus, no correlation could be found between compound activity and kDNA accumulation. The present results stimulate further investigations of this class of compounds for the rational design of new chemotherapeutic agents for Chagas disease

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An overview of Chagas disease treatment

Cited by 108 publications

References 1 publication

Preparation, characterization and evaluation of the in vivo trypanocidal activity of ursolic acid-loaded solid dispersion with poloxamer 407 and sodium caprate

Preparation, characterization and evaluation of the in vivo trypanocidal activity of ursolic acid-loaded solid dispersion with poloxamer 407 and sodium caprate

Ergosterol biosynthesis and drug development for Chagas disease

The biological in vitro effect and selectivity of aromatic dicationic compounds on Trypanosoma cruzi

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