Oral delivery of liver-targeting nanodrug against hepatic alveolar echinococcosis

Background:

Alveolar echinococcosis (AE) is a lethal parasitic disease which primarily affects the liver. Although continued efforts have been made to find new drugs against this orphan and neglected disease, the current treatment options remain limited, with drug delivery considered a likely barrier for successful treatment.

Materials and methods:

Nanoparticles (NPs) have gained much attention in the field of drug delivery due to their potential to improve delivery efficiency and targetability. In this study, biocompatible PLGA nanoparticles encapsulating a novel carbazole aminoalcohol anti-AE agent (H1402) identified in our previous study  were prepared to promote the delivery of the parent drug to liver tissue for treating hepatic AE.

Results:

H1402-loaded nanoparticles (H1402-NPs) had a uniform spherical shape and a mean particle size of 55 nm. Compound H1402 was efficiently encapsulated into PLGA NPs with a maximal encapsulation efficiency of 82.1% and drug loading content of 8.2%. An in vitro uptake assay demonstrated that H1402-NPs rapidly penetrated the vesicle wall and extensively accumulated in the metacestode vesicles of Echinococcus mulilocularis within only 1 h. The biodistribution profile of H1402-NPs determined through ex vivo fluorescence imaging revealed significantly enhanced liver distribution compared to unencapsulated H1402, which translated to improved therapeutic efficacy and reduced systemic toxicity (especially hepatotoxicity and cytotoxicity) in a hepatic AE murine model. Following a 30-day oral regimen (100 mg/kg/day), H1402-NPs significantly reduced the parasitic burden in both the parasite mass (liver and vesicle total weight, 8.8%) and average vesicle size (89.9%) compared to unmedicated infected mice (both p-values < 0.05); the treatment outcome was more effective than those of albendazole- and free H1402-treated individuals.

Conclusion:

Our findings demonstrate the advantages of encapsulating H1402 into PLGA nanoparticles and highlight the potential of H1402-NPs as a promising liver-targeting therapeutic strategy for hepatic AE.

Jun Li is a professor of Xinjiang Medical University and a senior research fellow of State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, China. She received her B. Sc from Xinjiang Medical University. In 2004, she obtained her PhD at the University of Queensland working on developing diagnosis tool for detecting cystic echinococcosis. She then spent 3 years working on PanBio for developing diagnosis kit for infectious diseases. From 2008-2013, she worked on molecular biology of Echinococcus as a senior research officer in Molecular Parasitology Laboratory, Infectious Diseases Division, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. She has published more than 80papers/articles in the international journals in her research career.