Significant improvement in bioavailability and therapeutic efficacy of mebendazole oral nano-systems assessed in a murine model with extreme phenotypes of susceptibility to Trichinella spiralis

This study aimed to analyze whether enhancement of the biopharmaceutical efficiency of mebendazole (MBZ), a poorly water-soluble anthelmintic drug, significantly improves its antiparasitic activity in a murine model of trichinellosis. Two advanced oral formulations were developed: polyvinyl alcohol-derived nanoparticles (NP) and β-cyclodextrin citrate inclusion complexes (Comp). The NP and Comp formulations' physicochemical characteristics, pharmacokinetics, in vitro anthelmintic activity, and in vivo therapeutic efficacy against Trichinella spiralis encysted muscle larvae were examined. The formulations showed smaller particle sizes and enhanced dissolution properties than pure MBZ. The pharmacokinetics studies indicate that NP and Comp significantly improved MBZ bioavailability. The in vivo activity was assessed during the parenteral stage of T. spiralis infection in male and female mice from two genetically distinct lines differing in mebendazole pharmacokinetic parameters and susceptibility to the parasite. Both NP and Comp significantly increased mebendazole's anthelmintic activity against the encysted parasites, which would be attributed to the improved MBZ absorption provided by these innovative formulations. The formulations overcome the drug's poor solubility and low bioavailability limitations, resulting in a higher plasma concentration of the active drug, even at low doses. In summary, these findings suggest that the newly designed mebendazole formulations are suitable for treating T. spiralis infection and highlight a potential improvement in the pharmacological treatment of trichinellosis.