In vitro efficacy of albendazole-loaded 13-cyclodextrin against protoscoleces of Echinococcus granulosus sensu stricto

Background: Cystic echinococcosis (CE), a widespread helminthic disease caused by the larval stage of the dog tapeworm Echinococcus granulosus represents a public health concern in humans. Albendazole (ABZ) is the first -line treatment for CE; however therapeutic failure of ABZ against CE occurs because of size and location of formed cysts as well its low aqueous solubility and consequently its erratic bioavailability in plasma. Serious adverse effects have also been observed following the long-term use of ABZ in vivo.Methods: We evaluated the apoptotic effects of ABZ-loaded 13-cyclodextrin (ABZ-13-CD) against protoscoleces (PSCs) versus ABZ alone. After 15 h of exposure, Caspase-3 enzymatic activity was determined by fluorometric assay in PSCs treated with ABZ and ABZ-13-CD groups. To assess the treatment efficacy of ABZ-13-CD against PSCs, mRNA expression of Arginase (EgArg) and Thioredoxin peroxidase (EgTPx) were quantified by Real-time PCR.Results: A significant scolicidal activity of ABZ was observed only at a concentration of 800 mu g/mL (100% PSCs mortality rate after 4 days of exposure), while the 200 and 400 mu g/mL ABZ reached 100% PSCs mortality rate after 9 sequential days. The 400 mu g/mL ABZ-13-CD had 100% scolicidal rate after 5 days of exposure. Morpho-logical alterations using scanning electron microscopy in treated PSCs revealed that 400 mu g/mL ABZ-13-CD induced higher Caspase-3 activity than their controls, indicating a more potent apoptotic outcome on the PSCs. Also, we showed that the 400 mu g/mL ABZ-13-CD can down-regulate the mRNA expression of EgArg and EgTPx , indicating more potent interference with growth and antioxidant properties of PSCs.Conclusions: In the present study, a significant scolicidal rate, apoptosis intensity and treatment efficacy was observed in PSCs treated with 400 mu g/mL ABZ-13-CD compared to ABZ alone. This provides new insights into the use of nanostructured 13 -CD carriers with ABZ as a promising candidate to improve the treatment of CE in in vivo models.