Acute and Subacute Toxicity of Sorbitan Monostearate (Span 60) Non-ionic Surfactant Vesicles (Niosomes) in Sprague Dawley Rats

This study was designed to determine the acute and subacute toxicity of non-ionic surfactant, sorbitan monostearate (Span 60) vesicles in a Sprague Dawley rat model. The primary aim was to investigate the acute toxicity of Span 60 niosomes after single intraperitoneal (IP) as well as once daily bolus dose for 5 days. Niosomes were prepared by the thin-film hydration method and subjected to ultracentrifugation to produce a final concentration of 30 mg of span 60 in 1 ml of niosome suspension. Acute toxicity study was performed following OECD test guideline 423 with modifications. Animals were divided into four groups, two control groups and two treatment groups. Group 1 animals were administered single 600 mg/kg IP bolus dose, whilst group 2 animals received 120 mg/kg/day IP for 5 days. The controls for each treatment group was administered an equivalent volume of phosphate buffered saline (PBS). Their body weight, food intake, water intake, fecal mass and urine output were measured daily. All clinical signs, time of onset, duration, and reversibility of toxicity or mortality were documented. Gross necropsies were performed on all animals terminated at 14 days post injection. There was no treatment related deaths and no toxic signs were observed in the two treatment groups. There was an initial decrease in food intake and, hence, body weight with IP niosome injection. However, weight loss was less than 10 percent in both groups of animals. All other parameters measured showed no statistical significance between niosome treated group and placebo. Necropsy performed at day 14 showed no signs of local reaction and there was no discernible effect on major organs. Results indicated that the LD50 of IP injected Span 60 was greater than 600 mg/kg. Therefore, Span 60-based niosomes appear to be non-toxic at the tested doses and experimental conditions and may not contribute to the potential toxicity of drug-loaded niosomes of this surfactant.