TOXICOLOGICAL EVALUATION OF KAURENOIC ACID AND ITS NANOLIPOSOMAL FORMULATION IN EXPERIMENTAL ANIMALS

Kaurenoic acid (KA), a diterpenoid with various therapeutic potentials, faces challenges in clinical translation due to poor solubility and bioavailability. Nanoliposomal formulations offer a promising solution to these limitations. This study aimed to evaluate the safety profile of both free kaurenoic acid and its nanoliposomal formulation in experimental animals. Nanoliposomes were prepared using the thin-film hydration method. Acute toxicity test was conducted using Swiss albino. Subacute toxicity was evaluated using male Wistar rats. Animals were orally administered KA and kaurenoic acid loaded nanoliposomes (KALNL) at doses of 4, 40, and 400 mg/kg daily for seven consecutive days. Haematological, biochemical analyses as well as histopathological examinations of the liver and kidneys were also performed. Acute toxicity study showed no lethal outcomes or behavioral changes up to 5000 mg/kg for either KA or KALNL, indicating an oral LD50 greater than 5000 mg/kg. Body weight gain remained normal and comparable to controls. The subacute toxicity assessment revealed no mortality, gross pathological findings, or overt toxicity in any of the treated groups in haematological and biochemical parameters. Histopathological examination confirmed preserved hepatic and renal architecture, with no signs of necrosis, fatty degeneration, inflammatory cell infiltration, degeneration, or congestion in the liver and kidney sections, even at higher doses. Both KA and KALNL demonstrated a favorable safety profile during acute and subacute toxicity evaluations in experimental animals, suggesting their potential for further development in therapeutic applications.