Liposomal-praziquantel: Efficacy against Schistosoma mansoni in a preclinical assay
2013
Frezza, Tarsila Ferraz | Gremião, Maria Palmira Daflon | Zanotti-Magalhães, Eliana Maria | Magalhães, Luiz Augusto | de Souza, Ana Luiza Ribeiro | Allegretti, Silmara Marques
Currently, schistosomiasis mansoni is treated clinically with praziquantel (PZQ). Nevertheless, cases of tolerance and resistance to this drug have been reported, creating the need to develop new drugs or to improve existing drugs. Considering the small number of new drugs against Schistosoma mansoni, the design of nanotechnology-based drug delivery systems is an important strategy in combating this disease. The aim of this study was to evaluate the activity of PZQ containing liposome (lip.PZQ) on S. mansoni, BH strain. Mice were treated orally with different concentrations of PZQ and lip.PZQ 30 and 45 days following infection. The number of worms, recovered by perfusion of the hepatic portal system, and the number of eggs found in the intestine and liver were analysed. Parasite egg counts were also performed. The most active formulation for all parameters was 300mg/kg of lip.PZQ, since as it decreased the total number of worms by 68.8%, the number of eggs in the intestine by 79%, and the number of hepatic granulomas by 98.4% compared to untreated controls. In addition, this concentration decreased egg counts by 55.5%. The improved efficacy of the treatment with lip.PZQ, especially when administered 45 days following infection, compared with the positive-control group (untreated) and the groups that received free PZQ, can be explained by greater bioavailability in the host organism; the preferred target of lip.PZQ is the liver, and lip.PZQ is better absorbed by the tegument of S. mansoni, which has an affinity for phospholipids.
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