Efficiency of flubendazole-loaded mPEG-PCL nanoparticles: A promising formulation against the protoscoleces and cysts of Echinococcus granulosus

Abstract

None of the existing drugs can effectively treat the human cystic echinococcosis. This study aimed to improve the efficacy of flubendazole (FLBZ) against the protoscoleces and cysts of Echinococcus granulosus by preparing polymeric FLBZ-loaded methoxy polyethylene glycol-polycaprolactone (mPEG-PCL) nanoparticles. The protoscoleces and microcysts were treated with FLBZ-loaded mPEG-PCL nanoparticles (FLBZ-loaded nanoparticles) and free FLBZ at the final concentrations of 1, 5, and 10 μg/mL for 27 and 14 days, respectively. The chemoprophylactic efficacy of the drugs was evaluated in experimentally infected mice. The nanoparticles were stable for 1 month, with an average size of 101.41 ± 5.14 nm and a zeta potential of −19.13 ± 2.56 mV. The drug-loading and entrapment efficiency of the FLBZ-loaded nanoparticles were calculated to be 3.08 ± 0.15% and 89.16 ± 2.93%, respectively. The incubation of the protoscoleces with the 10 μg/mL nano-formulation for 15 days resulted in 100% mortality, while after incubation with the 10 μg/mL free FLBZ, the viability rate of the protoscoleces was only 44.0% ± 5.22%. Destruction of the microcysts was observed after 7 days’ exposure to the FLBZ-loaded nanoparticles at a concentration of 10 μg/mL. The in vivo challenge showed a significant reduction in the weight and number of the cysts (P < 0.05) in the mice treated with the FLBZ-loaded nanoparticles, yielding efficacy rates of 94.64% and 70.21%, correspondingly. Transmission electron microscopy revealed extensive ultrastructural damage to the cysts treated with the FLBZ-loaded nanoparticles. The results indicated that the FLBZ-loaded nanoparticles were more effective than the free FLBZ against the protoscoleces and cysts of E. granulosus both in vitro and in vivo.