Innovative lead discovery strategies for tropical diseases

Nwaka, Solomon; Hudson, Alan L.

doi:10.1038/nrd2144

Cited by 494 publications

(435 citation statements)

References 54 publications

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“…Interestingly, the toxicity of the NQC-AmpB system was approximately 10 times less than that of free AmpB. In addition, the selectivity index (SI), an indicator of the selectivity of drugs tested in in vivo models (60) , was increased by 10-fold when AmpB was added to the proposed nanodelivery system. Because the nanoparticle formulations did not cause any hemolysis of human red blood cells (31) (Table 1), the study suggested that the NQCAmpB nanoparticles could be used as an AmpB delivery system to be evaluated in in vivo models against Leishmania spp.…”

Section: Optimized Nanoparticle Delivery Systems For Ampb Based On Chmentioning

confidence: 87%

New delivery systems for amphotericin B applied to the improvement of leishmaniasis treatment

Chávez-Fumagalli

Ribeiro

Castilho

et al. 2015

Rev. Soc. Bras. Med. Trop.

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Leishmaniasis is one of the six major tropical diseases targeted by the World Health Organization. It is a life-threatening disease of medical, social and economic importance in endemic areas. No vaccine is yet available for human use, and chemotherapy presents several problems. Pentavalent antimonials have been the drugs of choice to treat the disease for more than six decades; however, they exhibit high toxicity and are not indicated for children, for pregnant or breastfeeding women or for chronically ill patients. Amphotericin B (AmpB) is a second-line drug, and although it has been increasingly used to treat visceral leishmaniasis (VL), its clinical use has been hampered due to its high toxicity. This review focuses on the development and in vivo usage of new delivery systems for AmpB that aim to decrease its toxicity without altering its therapeutic efficacy. These new formulations, when adjusted with regard to their production costs, may be considered new drug delivery systems that promise to improve the treatment of leishmaniasis, by reducing the side effects and the number of doses while permitting a satisfactory cost-benefit rati

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Section: Optimized Nanoparticle Delivery Systems For Ampb Based On Chmentioning

confidence: 87%

New delivery systems for amphotericin B applied to the improvement of leishmaniasis treatment

Chávez-Fumagalli

Ribeiro

Castilho

et al. 2015

Rev. Soc. Bras. Med. Trop.

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“…Only those compounds that attain an SI value greater than 50 (Nwaka & Hudson 2006) will be considered for further screening. Next, a single drug concentration equivalent to 50X the parasite IC 50 of each compound will be assayed using the AlamarBlue TM protocol to evaluate the toxicity to mammalian cells (Appendix B).…”

Section: For In Vitro Models For Chagas Disease Drug Discovery and Dementioning

confidence: 99%

In vitro and in vivo experimental models for drug screening and development for Chagas disease

Romanha

Castro

Soeiro

et al. 2010

Mem. Inst. Oswaldo Cruz

308

339

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Chagas disease, a neglected illness, affects nearly 12-14 million people in endemic areas of Latin America. Although the occurrence of acute cases sharply has declined due to Southern Cone Initiative efforts to control vector transmission, there still remain serious challenges, including the maintenance of sustainable public policies for Chagas disease control and the urgent need for better drugs to treat chagasic patients. Since the introduction of benznidazole and nifurtimox approximately 40 years ago, many natural and synthetic compounds have been assayed against Trypanosoma cruzi, yet only a few compounds have advanced to clinical trials. This reflects, at least in part, the lack of consensus regarding appropriate in vitro and in vivo screening protocols as well as the lack of biomarkers for treating parasitaemia. The development of more effective drugs requires (i) the identification and validation of parasite targets, (ii) compounds to be screened against the targets or the whole parasite and (iii) a panel of minimum standardised procedures to advance leading compounds to clinical trials. This third aim was the topic of the workshop entitled Experimental Models in Drug Screening and Development for Chagas Disease, held in Rio de Janeiro, Brazil, on the 25th and 26th of November 2008 by the Fiocruz Program for Research and Technological Development on Chagas Disease and Drugs for Neglected Diseases Initiative. During the meeting, the minimum steps, requirements and decision gates for the determination of the efficacy of novel drugs for T. cruzi control were evaluated by interdisciplinary experts and an in vitro and in vivo flowchart was designed to serve as a general and standardised protocol for screening potential drugs for the treatment of Chagas disease

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“…An agreed set of product profiles that describe the target clinical efficacy, route of administration, dosage regimen, safety and cost of treatment are widely used in industry to drive lead discovery and candidate selection. Emphasis should be placed on understanding the product profile of drugs required for the various neglected diseases 3 .…”

Section: Global Portfoliomentioning

confidence: 99%

“…The TDR is now implementing a scalable, collaborative model for drug discovery that is based on networks and partnerships with industry and academia in developed and developing countries 3 . Scaling up or expanding innovative drug-discovery networks could be a way to mobilize resources from both public and private sectors.…”

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confidence: 99%