Hydatid cyst or cystic echinococcosis (CE) is well-known as one of the most common universal parasitic infections, which infects a wide range of hosts such as humans, wild animals, and domestic livestock. Therefore, CE can be considered as an important challenge both from medical and economic points of view.
2.10. Metal oxide NPs
Zinc oxide nanoparticles
ZnO nanoparticles are non-toxic and compatible with body skin. Properties such as skin adaptation, non-toxicity, antimicrobial, antiparasitic, and antifungal activity have made these nanoparticles a widely-used and important compound in manufacturing medicine. These nanoparticles, without toxic effects on healthy cells, induce death in cancer cells; studies have shown these nanoparticles can be used for gene delivery (66,67). Norouzi et al. recently investigated the protoscolicidal effects of zinc oxide nanoparticles for the first time. At 50 and 100 mg/ml concentrations, the highest protoscolicidal effects of this compound were observed in 10 min of zinc oxide and protoscolece nanoparticles exposure, which was 19.6% (very weak) and with no increase in performance over time; it was a low percentage, indicating this compound was not suitable for use in hydatid cyst surgery (28). In another study on this nanoparticle in 2015 by Razi Jalali et al., the protoscolicidal effects of zinc oxide and ABZ, Echinacea purpurea, and Sambucus ebulus nanoparticles were investigated, which revealed a decrease in size, volume, and number of cysts in all the compounds (37).
Titanium dioxide (TiO2) nanoparticles
TiO2 nanoparticles are considered as one of the most widely used nanoparticles in various industries such as cosmetics, food, and pharmaceuticals, since they have some physicochemical properties such as non-toxicity, cost-effectiveness, anticorrosive, high stability, photocatalytic properties, etc. These compounds kill cells by inactivating germ cell and DNA enzymes as well as by removing fluids from bacterial cells. Other uses of these compounds include treating and diagnosing cancer (68–70). Navvabi et al. (2019) recently investigated the in vitro and in viovo protoscolicidal effects of Echinometra mathaei (sea urchin gonad) extract alone or combined with Tio2 NPs. Their results showed that sea urchin gonad extract at the concentration 15 μg/ml, especially in combination with TiO2, killed 84% of the protoscoleces after 60 min exposure in vitro. On the other hand, oral administration of infected mice with the combination of the gonad extract + TiO2 for 3 months demonstrated higher efficacy by reduction in number, size and volume of the hydatid cysts in comparison to the control group (29).
Cerium dioxide nanoparticles
Cerium (Ce) is one of the rare-earth elements that, because of its special structure, has expended its use. Other features include its cost-effectiveness. Many studies have investigated the benefits of this nanoparticle, such as antimicrobial, anti-cancer, treatment, and antioxidant activities (71,72). In the study by Aryamand et al (2019), the in vitro and in vivo protoscolicidal effects of Holothuria leucospilota extract alone, CeO2 nanoparticles alone, and extract combined with CeO2 NPs were investigated for 10 to 60 min. In vitro results showed that the most protoscolicidal effects were reported for extract (70% at 20 mg/ml for 60 min), followed by the combination of this extract and Ce nanoparticles (63% in 15 mg/ml concentration for 1 h). Also, in vivo assay demonstrated that all three compounds significantly reduced the number and size of the hydatid cysts compared to the control group that received no treatment (30).
Zirconium dioxide nanoparticles
Zirconium (Zr) is a chemical element that has some applications, especially in medicine and dentistry (73). Zirconium dioxide (ZrO2), also called zirconia, has some unique properties such as high compatibility, low toxicity, low cost, and high strength and is broadly used in various biomedical fields including antimicrobial ones (74-77). In the study conducted by Ibrahim (2020), ZrO2 at the concentrations of 1000, 2000, and 4000 µg/ml significantly killed 49.6, 52.7, and 53.1% of the hydatid protoscoleces after 60 min (31).
4.11. Nanopolymeric particles
Various properties of chitosan nanoparticles (Ch NPs) including non-toxicity, water solubility, stability, simple preparation, environmental compliance, and antimicrobial activity have made them remarkable and effective compounds in the field of medicine. In the field of vaccine development, several studies have been performed to evaluate the usefulness of these nanoparticles, showing their beneficial effects (78-80).
Chitosan–curcumin nanoparticles
In another study by Napooni et al. (2019), the in vitro protoscolicidal effects of chitosan–curcumin nanoparticle (Ch-Cu NPs) at different concentrations of 0.25, 0.05, 1, 2, and 4 mg/mL were evaluated for 5, 10, 20, 30, and 60 min. The results showed that the highest mortality rate (68%) of protoscoleces was observed after exposure to Ch-Cu-NPs at the concentration of 4000 µg/ml for 60 min, whereas by scanning electron microscopy, the length and width of protoscoleces were significantly reduced compared to the control group (32).
Chitosan-praziquantel and -albendazole nanoparticles
Torabi et al. (2018) examined the protoscolicidal, prophylactic and therapeutic effects of ChPZQ and ChABZ. In evaluating the in vitro protoscolicidal effects of these compounds, microcysts were exposed (for 16 days) at the concentrations of 1, 5, and 10 μg/ml of chitosan-praziquantel (ChPZQ) and -albendazole (ChABZ); then, it was observed that the best effect during this time was related to using these two compounds together (at concentrations 5 and 10) when no microcysts were observed for 10 days post-incubation. Compared to ChPZQ and ChABZ, ChPZQ performed better at all the three concentrations than ChABZ (no significant difference). In order to evaluate the therapeutic and prophylactic effects of these compounds, the number and weight of cysts in contact with the above compounds were evaluated. For evaluating the prophylactic effect of these compounds, a significant decrease in the number and weight of cysts in the group receiving the two compounds was observed compared to the control group receiving no medication. However, in the evaluation of therapeutic effect, there was a significant difference in the number of cysts in the group receiving ChABZ and ChPZQ nanoparticles together compared to the control group; but no significant decrease was observed in the weight of the cysts compared to the control group. In the mice receiving both combinations, GL and LL were separated (81). Also, in another study by Torabi et al., ChPZQ showed more stability than ChABZ, which could be due to its better performance (66). In the recent study conducted by Darvishi et al. (2020), the effects of ABZ-sulfoxide (SO)-loaded chitosan (CS)-PGLA NPs synthesized by nanoprecipitation orally administered at the dose of 10 mg/kg/day for 45 days showed the significant therapeutic effect in the weight and volume of cysts in comparison to that in the control group, indicating that ABZ-SO-loaded CS-PGLA NPs could improve the therapeutic effects of ABZ-SO in the CE treatment in mice (36).
Albendazole sulfoxide-loaded PLGA-PEG NPs
In 2016, Naseri et al. investigated the protoscolicidal effects and apoptotic activity of albendazole sulfoxide-loaded PLGA-PEG (ABZs-loaded PLGA-PEG). In this study, the concentrations of 50, 100, 150, and 200 μg/ml of these compounds were exposed to the specific concentration of hydatid cyst fluid for 5 to 60 min. For evaluating the protoscolicidal effects, it was observed that at the concentrations of 150 and 200 μg/ml, the nanodrug (at all times of the experiment) had 100% protoscolicidal effects, while at the concentration of 200 μg/ml, albendazole at 30 min had a 100% effect. Protoscoleces treated with ABZs-loaded PLGA-PEG showed surface shrinkage, disoriented appearance, and a disrupted characteristic due to programmed cell death. Both compounds had apoptotic intensity, but no significant difference was observed in the activity of both compounds (34).
Flubendazole-loaded mPEG-PCL NPs
In 2018, studies on the protoscolicidal effects of flubendazole-loaded mPEG-PCL NPs were conducted by Farhadi et al. The in vitro study showed that, at the exposure time of 27 days, 10 μg/ml of these nanoparticles was able to kill all the protoscoleces on the 15th day. In vivo studies also showed that the number of cysts was significantly lower than the control group, but the difference in the number of cysts in the free flobendazole recipient group and the group that received nanoparticle was not significant. The weight of the cysts in the nanoparticle receiving group was much lower than other groups; the cysts underwent many changes and there were marked ultrastructural changes in the germinal layer (35).
Conclusion
The results of this review study showed the high efficacy of a wide range of organic and inorganic NPs against CE, indicating that nanoparticles could be considered as an alternative and complementary resource for CE treatment. The results demonstrated that the most widely used nanoparticles for hydatid cyst treatment were metal nanoparticles, metal oxide nanoparticles, followed by polymeric nanoparticles. We found that the most compatible drugs with nanoparticles were albendazole, followed by praziquantel and flubendazole, indicating a deeper understanding about the synergistic effects of nanoparticles and the present anti-parasitic drugs to treat hydatid cyst. The important point about using these nanoparticles is their toxicity; therefore, cytotoxicity, as well as acute and chronic toxicities of these nanoparticles, should be considered in particular. As a limitation, in the present study, although most studies have been performed in vitro, more studies are needed to confirm the effect of these nanoparticles as well as their exact mechanisms in the hydatid cyst treatment, especially in animal models and clinical settings.
This entry is adapted from the peer-reviewed paper 10.3390/nano10122538