Amorphous ivermectin nanoparticles: in vitro and in vivo studies supporting their potential in neurocysticercosis therapy

Abstract

Neurocysticercosis is a serious parasitic infection of the central nervous system caused by the larval stage of Taenia solium, and is an important public health concern in many countries of Asia, Latin America, and Africa. In the last decade have seen a significant increase in diagnosed cases in Europe and North America, due to immigration from countries where the disease is endemic. Although ivermectin has demonstrated antiparasitic efficacy, its therapeutic potential against neurocysticercosis is limited by poor solubility and bioavailability. Therefore, this study aimed to develop ivermectin nanosuspensions as a promising strategy to enhance its solubility and overall antiparasite efficacy. Ivermectin nanosuspensions were prepared using the antisolvent precipitation method with SOLUPLUS® and polyvinylpyrrolidone as stabilizers. In vivo studies were conducted to evaluate whether the ivermectin nanosystems could alter the parasite's energy metabolism, ultimately leading to its death. The findings indicated that the nanoparticles were obtained in high yields. In the solid state, these nanosystems showed an almost complete drug amorphization after the spray-drying process. After drying and redispersion, these formulations exhibited particle sizes between 76 and 100 nm and zeta potential values between −2.0 and −23.1, depending on the type of stabilizer. The in vivo study indicated that several metabolic alterations were observed in Taenia crassiceps cysticerci after in vivo treatment with nanosuspensions of ivermectin. These findings confirm that the formulated ivermectin nanosuspensions effectively reduced metabolite concentrations linked to glycolysis, mitochondrial function, protein catabolism, and fatty acid metabolism. This suggests a promising strategy to enhance drug efficacy for the successful treatment of neurocysticercosis.