Preclinical evaluation of oral nanoformulation based on natural extract as a potential treatment for type 2 diabetes mellitus: preliminary data.

Previous studies have shown that an oral nanoformulation (ONF) based on natural extracts, ursolic acid (104.3 μM), oleanolic acid (30.8 μM) and ursolic acid lactone (35.8 μM) obtained by hexane: methanol: water 4:3:1(v/v) extraction from Eucalyptus tereticornis leaves reduces metabolic alterations in a diet- induced obese (DIO) mouse model. The present work aims to develop preclinical safety and biological efficacy tests for the ONF, following the recommendations established by the Organization for Economic Cooperation and Development guidelines.

The ONF was scaled up from the previously described protocol characterised, and carbohydrate metabolism was evaluated in the DIO mouse model. Three groups were established: ONF, empty nanoparticles (NPs) and vehicle.

Acute oral toxicity: Three Wistar rats were given a single dose of 2000 mg/kg of ONF. The animals were monitored daily for 14 days. Repeated dose oral toxicity for 28 days: Five male and five female Swiss mice were treated daily for 28 days with one dose of 218ug/kg (ONF). In the end, they remained under observation for two weeks. At the endpoint, blood samples for hemogram and blood chemistry were taken. A necropsy was also performed, and samples of the internal organs were taken for histopathological analysis.

There were no clinical signs of disease or signs suggestive of toxicity and weight gain remained stable; no organ abnormalities were observed. Renal and liver function tests, ionogram and haem-leukogram were within normal ranges.

The preliminary results show that ONF with anti-obesogenic activity and potential anti-diabetic activity is biologically effective and safe in experimental animals.

 

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Publication History

Article published online:
16 November 2023