PLGA - encapsulated harmine derivative H-2-168: A promising therapeutic agent for mitigating liver damage in hepatic hydatid disease

Harmine (HM), a bioactive alkaloid, exhibits remarkable antiparasitic potency. Nevertheless, its translational potential is substantially constrained by neurotoxicity, necessitating the development of safer analogs. H-2-168, a rationally designed derivative synthesized via targeted structural modifications of the HM core, has emerged as a leading candidate for further therapeutic exploration due to its favorable pharmacological profile. To optimize its pharmacokinetic properties and enhance treatment efficacy, this study reports the fabrication of H-2-168-loaded poly (lactic - co - glycolic acid) (PLGA) nanoparticles (H8-PLGA-NPs). Results demonstrated that H8-PLGA-NPs exhibited uniform spherical morphology with an average diameter of 198 nm (PDI = 0.15) and a high drug encapsulation efficiency of 88.6%. Following 30-day oral administration (100 mg/kg/day), H8-PLGA-NPs demonstrated significantly enhanced anthelmintic efficacy and tissue regenerative capacity compared to free H-2-168, while effectively ameliorating inflammatory responses and hepatic fibrosis progression. Notably, systemic toxicity was substantially reduced, particularly hepatotoxicity and cytotoxicity. This study substantiates that PLGA-based nanocarriers markedly improve the therapeutic outcomes of H-2-168 against cystic echinococcosis (CE) through optimized drug encapsulation and delivery efficiency, thereby proposing a promising therapeutic strategy for CE management. Nevertheless, comprehensive investigations into the long-term biosafety profiles of these nanoparticles and optimal dosing regimens warrant further exploration.