Nanotechnology-Formulated Ivermectin for Enhanced Gastrointestinal Nematode Control in Sheep: Pharmacokinetic and Pharmacodynamic Evaluation Under Nigerian Conditions

The escalating prevalence of ivermectin resistance in gastrointestinal nematodes of sheep in Nigeria necessitates innovative drug delivery strategies to improve efficacy at reduced doses while limiting resistance selection pressure. Nanoformulation using polymeric or lipid nanocarriers can enhance drug bioavailability, prolong systemic exposure, and improve drug penetration into refugia tissues. This study developed, characterised, and evaluated a poly-lactic-co-glycolic acid nanoformulated ivermectin preparation for use in Yankasa and Uda sheep under Nigerian field conditions, with pharmacokinetic and pharmacodynamic studies conducted in Kano and Sokoto states respectively. Ivermectin-loaded PLGA nanoparticles were synthesised by double emulsion solvent evaporation, characterised for particle size, zeta potential, encapsulation efficiency, and in vitro release. Comparative pharmacokinetic studies were conducted in 24 sheep receiving conventional ivermectin at 0.2 mg/kg or nanoformulated ivermectin at 0.1 and 0.2 mg/kg subcutaneously. Pharmacodynamic evaluation was performed using faecal egg count reduction testing against naturally acquired Haemonchus contortus and Trichostrongylus species infections in 60 sheep on farms in Sokoto State. Nanoparticle characterisation showed mean size of 248 nm, zeta potential of minus 28 mV, and encapsulation efficiency of 91.4 percent. The nanoformulation at 0.2 mg/kg achieved significantly higher area under the curve and maximum concentration compared with conventional formulation, with prolonged terminal half-life of 14.3 versus 9.8 days. Faecal egg count reduction was significantly higher for nanoformulation at equivalent doses. These outcomes validate nanoformulated ivermectin as a promising strategy to overcome pharmacokinetic limitations and potentially delay resistance development in Nigerian small ruminant helminth management. Keywords: nanoformulation, ivermectin, pharmacokinetics, Haemonchus contortus, sheep.