In vitro efficacy of albendazole-loaded ß-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 ß-cyclodextrin (ABZ-ß-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-ß-CD groups. To assess the treatment efficacy of ABZ-ß-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 µg/mL (100% PSCs mortality rate after 4 days of exposure), while the 200 and 400 µg/mL ABZ reached 100% PSCs mortality rate after 9 sequential days. The 400 µg/mL ABZ-ß-CD had 100% scolicidal rate after 5 days of exposure. Morphological alterations using scanning electron microscopy in treated PSCs revealed that 400 µg/mL ABZ-ß-CD induced higher Caspase-3 activity than their controls, indicating a more potent apoptotic outcome on the PSCs. Also, we showed that the 400 µg/mL ABZ-ß-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 µg/mL ABZ-ß-CD compared to ABZ alone. This provides new insights into the use of nanostructured ß-CD carriers with ABZ as a promising candidate to improve the treatment of CE in in vivo models.

Nanoliposomes increases Anti-Trichomonas vaginalis and apoptotic activities of metronidazole.

Trichomoniasis, caused by Trichomonas vaginalis (T. vaginalis), is the most common non-viral sexually transmitted disease worldwide. As current trichomoniasis chemotherapies have many side effects, we examined the Anti-Trichomonas effects of nano-liposomal metronidazole (NLMTZ) compared to metronidazole (MTZ) in vitro. Liposomes were produced using the thin film hydration-sonication technique with a slight modification coated with MTZ. The average hydrodynamic diameter of monodispersed NLMTZ was evaluated by DLS and the morphological measurements were performed by scanning electron microscopy (SEM). The effects of NLMTZ and MTZ (5, 10, 20 and 40 µg/mL) on T. vaginalis trophozoites (105 cells/mL) in trypticase-yeast extract-maltose (TYM) medium were evaluated in different exposure times. Then, cell viability, IC50, SEM analysis and the expression of the metacaspase gene were assessed by qRT-PCR. Growth inhibition of MTZ in a concentration of 40 µg/mL was 39.34% after 3 h, whereas NLMTZ caused 51% growth inhibition after 3 h and lysed Trichomonas completely after 12 h. The IC50 values were estimated at 31.51 and 15.90 µg/mL after a 6 h exposure for MTZ and NLMTZ, respectively. Moreover, both T. vaginalis treated with MTZ and NLMTZ had high levels of metacaspase mRNA expression relative to the control groups (P< 0.05). A significant difference was observed between the apoptotic intensities of T. vaginalis treated with MTZ and NLMTZ (P< 0.05). This study showed that nano-liposomal MTZ is a potentially excellent approach for the treatment of trichomoniasis in vitro, although further studies are needed before consideration of clinical trials.

Recent advances on innate immune pathways related to host-parasite cross-talk in cystic and alveolar echinococcosis.

Cystic echinococcosis (CE) and alveolar echinococcosis (AE) are life-threatening parasitic infections worldwide caused by Echinococcus granulosus (sensu lato) and E. multilocularis, respectively. Very little is known about the factors affecting innate susceptibility and resistance to infection with Echinococcus spp. Although benzimidazolic drugs against CE and AE have definitively improved the treatment of these cestodes; however, the lack of successful control campaigns, including the EG95 vaccine, at a continental level indicates the importance of generating novel therapies. This review represents an update on the latest developments in the regulatory functions of innate immune pathways such as apoptosis, toll-like receptors (TLRs), and inflammasomes against CE and AE. We suggest that apoptosis can reciprocally play a bi-functional role among the host-Echinococcus metabolite relationships in suppressive and survival mechanisms of CE. Based on the available information, further studies are needed to determine whether the orchestrated in silico strategy for designing inhibitors and interfering RNA against anti-apoptotic proteins and TLRs would be effective to improve new treatments as well as therapeutic vaccines against the E. granulosus and E. multilocularis.

Therapeutic efficacy of nanocompounds in the treatment of cystic and alveolar echinococcoses: challenges and future prospects.

Echinococcus granulosus sensu lato and E. multilocularis are the causative agents of life-threatening cystic and alveolar echinococcoses (CE and AE), respectively, which lead to serious public health concerns across the globe. Benzimidazoles (BMZs) are the drugs of choice for the treatment of human CE and AE. Presently, the chemotherapeutic failures of BMZs against CE and AE are caused by their low aqueous solubility, poor absorption, and consequently their erratic bioavailability. Among the BMZ compounds used for CE/AE treatment, albendazole (ABZ) and mebendazole (MBZ) are the only drugs licensed for human use. Nevertheless, the administration of these BMZs for a long period of time leads to undesirable adverse effects. Therefore, there is an urgent need for designing new formulations of BMZs with increased bioavailability. To bridge these therapeutic gaps, nanoparticle enantiomers of ABZ and drug delivery systems based on nanostructured entities currently provide an interesting new formulation of already existing drugs to improve the pharmacokinetic effects of BMZs. This study provides an overview of the tested nanocompounds against E. granulosus and E. multilocularis, including their effective dose, type of nanoparticles (NPs), assay setting, and therapeutic outcomes. This review suggests that BMZ derivatives loaded in NPs can significantly improve the scolicidal and cysticidal activities compared with single BMZ. Moreover, BMZ-loaded polymeric NPs show a tendency to increase mortality rate against protoscoleces and microcysts compared with metallic formulations, nanoemulsions, lipid nanocapsules, solid lipid NPs, liposomes, and nanocrystals. In the future, the use of the newly structured entities, attained by bridging ligands to the modified surface of NPs, as well as the electromagnetically produced nanodrugs could be helpful for developing fine-tuned formulations as an alternative to the already existing drugs against these neglected parasitic infections.