Evaluation of a nanoformulation’s chronic and pre-chronic toxicity based on natural extracts for potential use in treating obesity-associated complications

An oral nanoformulation (ONF) based on natural extracts (OBE100); ursolic acid, oleanolic acid, and ursolic acid lactone, obtained by hexane: methanol: water 4:3:1(v/v) extraction from Eucalyptus tereticornis Sm. (Myrtaceae) leaves reduce metabolic alterations in a diet-induced obese mouse model [ 1 ]. The work aims to develop preclinical safety and biological efficacy tests for the ONF. The findings of acute oral toxicity, oral toxicokinetics, and repeated doses of oral toxicity for 28 days indicate that the compound ONF is safe based on clinical and paraclinical evaluation and histopathological analysis. To continue evaluating the in vivo safety profile of the ONF, we conducted sub-chronic toxicity studies for 90 days and a combined chronic toxicity/carcinogenicity study. These studies were carried out according to OECD guidelines [ 2 ]. In the sub-chronic toxicity study, the histopathological analysis of the stomach, liver, spleen, kidneys, small intestine, and testicles did not show any representative lesions between groups or associated with toxicity, providing strong evidence of the compound’s safety. Paraclinical tests and clinical follow-up did not present any abnormalities, further reinforcing the safety of the compound. For the combined chronic toxicity/carcinogenicity study, the following organs were taken: adrenal glands, spleen, brain, cerebellum, heart, esophagus, stomach, salivary glands, liver, small intestine, colon, lymph node, eyeball, pancreas, skin, lung, kidneys, uterus, testicles, gallbladder, ovaries, epididymis, seminal vesicle, prostate. A total of 2320 tissues are being processed. The results of the clinical evaluation, blood chemistry, and blood count did not show any toxicity associated with the treatments. No histopathological or neoplastic lesions have been observed. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany