Piperine-Loaded Nanoparticles: In Vitro Evaluation of a Botanical Nanoixodicide Against Rhipicephalus microplus and Amblyomma mixtum Larvae Resistant to Conventional Treatments

Background/Objectives: Tick infestations represent a major economic problem for livestock farming due to the hematophagous nature of these parasites and their crucial role as vectors of pathogens. The prolonged use of synthetic chemical ixodicides has led to resistance, prompting the search for alternative tick-control strategies. In this study, piperine-loaded polymeric nanoparticles were successfully developed using Eudragit® L100-55 (NP_Pip_1) and Eudragit® RLPO (NP_Pip_2) polymers, which were physicochemical characterized and evaluated against Rhipicephalus microplus and Amblyomma mixtum larvae resistant to conventional treatments. Methods/Results: NP_Pip_1 and NP_Pip_2 exhibited mean particle sizes of 107.30 ± 6.34 nm and 101.00 ± 1.51 nm, polydispersity index (PDI) values of 0.08 ± 0.02 and 0.05 ± 0.03, ζ potentials of −5.78 ± 2.14 and 32.7 ± 0.74 mV and encapsulation percentages (%E) of 17.44 ± 1.56 and 1.43 ± 0.11. The encapsulation efficiencies (%EE) were 69.76 ± 6.25% and 37.40 ± 2.89%, respectively. Free piperine showed LC50 and LC90 values of 1822.25 and 5981.74 µg/mL against R. microplus, and 1904.18 and 6213.28 µg/mL against A. mixtum. In contrast, NP_Pip_1 reduced LC50 and LC90 values by 1.83- and 2.2-fold against R. microplus and by 1.61- and 1.44-fold against A. mixtum, indicating improved ixodicidal activity compared with free piperine. NP_Pip_2 showed smaller reductions in LC50 and LC90 of 1.34- and 1.33-fold against R. microplus and 1.43- and 1.41-fold against A. mixtum. Conclusions: These results demonstrate that incorporating piperine into polymeric nanoparticles significantly improves its ixodicidal activity against resistant tick larvae, positioning this platform as a promising strategy for the development of alternative treatments against ticks resistant to conventional treatments.