Abstract
The alveolar echinococcosis of human is a severe helminthic disease caused by the larva of Echinococcus multilocularis tapeworms. Novel compounds or therapy strategies for the treatment of alveolar echinococcosis are urgently needed due to the limitation of the widely used albendazole. Magnetic microspheres as drug carriers in magnetically targeted therapy of tumor have gained growing interests advantaged by delivering the drug to the aimed site, achieving localized therapeutic effect effectively under the influence of an external magnetic field. In this study, we formulated magnetic microspheres loaded with E2-a (PLGA-Fe-E2-a) and identified the activity in E. multilocularis-infected mice which infected with 3,000 protoscoleces intraperitoneally. Compared with the untreated control, with the help of a magnet, there was a significant reduction in parasite burden with PLGA-Fe-E2-a treatment and similar reduction observed with albendazole. PLGA-Fe-E2-a treatment group also showed a significant increase in the IFN-γ level and impaired morphological and ultrastructural alterations. Most importantly, one-third concentrations of E2-a from PLGA-Fe-E2 based on the release profile of E2-a was equally effective in inhibiting metacestode growth as E2-a treated group, supporting efficacy and bioavailability of a drug. It will be an alternative treatment for alveolar echinococcosis using magnetic microspheres as drug carriers.
Highlights
The alveolar echinococcosis of human is a severe helminthic disease caused by the larva of Echinococcus multilocularis tapeworms
The PLGA-Fe-E2-a, magnetic microspheres loaded E2-a, were spherical with comparatively smooth surfaces evidenced by scanning electron micrographs (SEM) (Fig. 1A)
The PLGA-Fe-E2-a showed a monomodal population at diameter of 2.315 μm with polydispersity index (PDI) of 0.312 and zeta potential of − 3.59 mV, respectively (Fig. 1B,C)
Summary
The wet weight of metacestodes reduced significantly in abendazole (ABZ), PLGA-Fe-E2-a or E2-a treated group when compared to the untreated control group, respectively (2.59 ± 0.6 g, 2.72 ± 0.52 g and 3.57 ± 0.57 g versus 5.12 ± 1.51 g, p < 0.05) (Table 1). In the untreated control group, the metacestodes presented a larger number of small vesicles and more blood vessels compared with that in the ABZ and PLGA-Fe-E2-a treated groups (Fig. 2A). It was noted that the cysts from the untreated control group appeared intact and densely packed with morphologically different cells (Fig. 2C,D). In the ABZ group, we observed that the metacestodes were conglomerated with the swollen laminated layer and reduced cells of the germinal layer (Fig. 2). There was no statistical difference in the level of TGF-β in all groups (p > 0.05) (Table 1)
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