Oral Mucosa and Subacute Systemic Toxicity of Anacardic Acids‑Loaded Zein Nanoparticles

Anacardic acid, a bioactive chemical from the cashew shell liquid of Anacardium occidentale L., Anacardiaceae, is a promising oral antimicrobial agent, lacking complete toxicity evaluation. This study aimed to evaluate the oral mucosal and systemic toxicity of zein nanoparticles containing anacardic acid in vivo. Female mice (c57bl/6j) were treated orally and topically for 30 days and divided into four groups: I) negative control (saline solution); II) standard (chlorhexidine gluconate 0.12%); III) anacardic acids-loaded zein nanoparticles (9.337 µg/ml); and IV) blank zein nanoparticles. Weight variation, relative organs weight, and the thickness of target organs were analyzed. Groups III and IV showed the greatest weight loss, although without difference in kidneys, lungs, liver, and spleen weights. Groups III (0.16 ± 0.01 g) and IV (0.16 ± 0.02 g) presented lower cardiac mass than group I (0.21 ± 0.01 g) (p = 0.045). Buccal mucosa thickness was lower in groups III (562.9 ± 49.9 μm) and IV (627.6 ± 43.2 μm) than group II (1686.4 ± 220.2 μm) (p < 0.001). Ultimately, the administration of anacardic acids-loaded nanoparticles reduced cardiac mass but showed no other systemic toxicity signs. Additionally, oral mucosa toxicity was similar to or less severe than in the chlorhexidine-treated standard group.