No abstract

Alveolar echinococcosis (AE) is a chronic infectious parasitic disease that is fatal and still being neglected. Currently, the AE treatment recommended by the WHO is complete excision of the lesions, followed by the oral administration of albendazole (ABZ), the only effective first-line anti-AE drug, for two years. Unfortunately, complete excision of AE lesions is impossible in most cases, leaving the long-term use of ABZ as the only alternative. However, only about one-third of patients experience complete remission or cure with such treatments, largely because of the low oral bioavailability of ABZ caused by its very low solubility. To improve the oral bioavailability of ABZ, a novel nanocrystalline (NC) formulation of ABZ was obtained by spray-drying ABZ with a triblock copolymer poly­(ethylene oxide)-poly­(propylene oxide)-poly­(ethylene oxide) (Poloxamer 188), and its physical structure was confirmed by scanning electron microscopy (SEM), small-angle X-ray scattering (SAXS), wide-angle X-ray diffraction (WAXRD), and polarized optical microscopy (POM). The significantly reduced ABZ crystallite size coupled with prolonged ABZ supersaturation significantly improved the drug dissolution performance compared with that of the commercial ABZ oral product (Albenda), and the NC formulation showed an approximately 4.2-fold higher AUC than Albenda in a pharmacokinetic comparison in Beagle dogs as measured by the plasma concentration of albendazole sulfoxide, the active antiparasitic metabolite. Even more encouragingly, after 30 days of once-daily oral administration of the NC and Albenda formulations to SD rats with hepatic alveolar echinococcosis, the NC formulation demonstrated a cyst inhibition effect 3.7-fold greater than that of Albenda. We therefore conclude that the NC formulation could potentially be developed into an improved anti-AE drug therapy.

Echinococcosis is a worldwide anthropozoonosis which is highly endemic over large animal husbandry areas in northwestern China. The current clinical therapeutic medicine against echinococcosis is albendazole, although it caused serious side effects in patients. The component in traditional Chinese herb medicine, Sophora moorcroftiana alkaloids (SA), is thought to be a potential drug to treat echinococcosis. In order to explore the effect and mechanism of SA treatment against echinococcosis, we established animal echinococcosis model and treated rats with albendazole alone, alkaloids alone, and combined therapy. The combined treatment showed effective inhibition against parasite infection due to induction of host response and alleviated liver injury; meanwhile albendazole caused serious liver problem. The proteomics study revealed that the combined therapy might induce complement activation through C3, C4, C5, SERPINA1, and SERPINC1 proteins and cell adhesion by ANXA2, EZR, YWHAB, HSP90AN1, and PRKAR2A proteins, while albendazole treatment could induce liver injury through CRYAB, YWHAZ, SLC25A24, and HSPA1B proteins that were involved in cell death. In all, we consider that the combinational treatment displayed better therapeutic effects against liver echinococcosis as well as alleviated liver injury, which could be considered as an effective strategy to treat echinococcosis clinically.

Background Hepatic alveolar echinococcosis (HAE) is caused by the growth of Echinococcus multilocularis larvae in the liver. It is a chronic and potentially lethal parasitic disease. Early stage diagnosis for this disease is currently not available due to its long asymptomatic incubation period. In this study, a proton nuclear magnetic resonance ( 1 H NMR)-based metabolomics approach was applied in conjunction with multivariate statistical analysis to investigate the altered metabolic profiles in blood serum and urine samples obtained from HAE patients. The aim of the study was to identify the metabolic signatures associated with HAE. Results A total of 21 distinct metabolic differences between HAE patients and healthy individuals were identified, and they are associated with perturbations in amino acid metabolism, energy metabolism, glyoxylate and dicarboxylate metabolism. Furthermore, the present results showed that the Fischer ratio, which is the molar ratio of branched-chain amino acids to aromatic amino acids, was significantly lower ( P < 0.001) in the blood serum obtained from the HAE patients than it was in the healthy patient group. Conclusions The altered Fischer ratio, together with perturbations in metabolic pathways identified in the present study, may provide new insights into the mechanistic understanding of HAE pathogenesis and potential therapeutic interventions. Electronic supplementary material The online version of this article (10.1186/s13071-019-3554-0) contains supplementary material, which is available to authorized users.