LAUSR

Abstract Methotrexate (MTX) has been often formulated as nano and micro-emulsions, nominally to address its poor solubility and off-target effects. Nanoformulated MTX is universally reported to be a more efficacious anti-cancer agent than direct-dissolved drug; however, these investigations generally fail to screen for in vivo toxicity. This study aims to remedy this oversight. MTX was formulated as a standard Pluronic oil-in-water microemulsion with good drug encapsulation efficiency (73.0% ± 8.4). Preliminary in vitro free radical scavenging studies found that formulation reduces drug oxidation four-fold. The toxic effects of formulated and unformulated MTX were investigated in a Wistar rat model. Rats received 0.05 mg/kg MTX as either the microemulsion or directly dissolved in phosphate-buffered saline. A drug-free microemulsion, PBS solution, and saline solution were used as controls. After 28 days, serum levels of enzymes indicative of kidney and liver damage were quantified. Significantly higher serum liver, and serum kidney enzymes were observed in the rats that received the directly dissolved MTX drug (P