Pre-clinical toxicity assessment of Artemisia absinthium extract-loaded polymeric nanoparticles associated with their oral administration

• Published in: Frontiers in pharmacology 2023-07, Vol.14, p.1196842-1196842
• Main Authors: Kauser, Sana, Mughees, Mohd, Swami, Sanskriti, Wajid, Saima
• Format: Article
• Language: English
• Subjects: acrylic acid; Artemisia absinthium; LD50; N-isopropyl acrylamide; N-vinyl pyrrolidone; Pharmacology; polymeric nanoparticles
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2023.1196842

This study was designed to quantify the composition of the ethanolic extract of through gas chromatography-mass spectrometry analysis and ensure safety of extract-loaded polymeric nanoparticles (ANPs) before considering their application as a drug carrier via the oral route. We synthesized N-isopropylacrylamide, N-vinyl pyrrolidone, and acrylic acid crosslinked polymeric NPs by free-radical polymerization reaction and characterized them by Fourier-transform infrared spectroscopy, transmission electron microscopy, and dynamic light scattering spectroscopy. Different concentrations of extract (50 mg/kg, 300 mg/kg, and 2,000 mg/kg body weight) were encapsulated into the hydrophobic core of polymeric micelles for the assessment of acute oral toxicity and their LD50 cut-off value as per the test procedure of OECD guideline 423. Orally administered female Wistar rats were observed for general appearance, behavioral changes, and mortality for the first 30 min, 4 h, 24 h, and then, daily once for 14 days. ANPs at the dose of 300 mg/kg body weight were used as an initial dose, and rats showed few short-lived signs of toxicity, with few histological alterations in the kidney and intestine. Based on these observations, the next set of rats were treated at a lower dose of 50 mg/kg and a higher dose of 2,000 mg/kg ANPs. Rats administered with 50 mg/kg ANPs remained normal throughout the study with insignificant histological disintegration; however, rats treated at 2,000 mg/kg ANPs showed some signs of toxicity followed by mortality among all three rats within 24-36 h, affecting the intestine, liver, and kidney. There were no significant differences in hematological and biochemical parameters among rats treated at 50 mg/kg and 300 mg/kg ANPs. We conclude that the LD50 cut-off value of these ANPs will be 500 mg/kg extract loaded in polymeric NPs.