Toxicity Profile of Solvents by Aspiration Approach for Topical Agent Delivery to Respiratory Tract Epithelium

Abstract

Agent solubility is a problem for aspiration of agents into lungs for chemopreventive efficacy evaluation, since many agents have to be dissolved in solvents. These solvents may be toxic to the lung epithelium. A study was conducted in female A/J mice to determine toxicity of different solvent concentrations by using saline, dimethyl sulfoxide (DMSO), ethanol, polyethylene glycol 400 (PEG-400), and labrasol for 1, 5, and 28 days via aspiration route. Toxicity was determined by measuring changes in body weight and bronchoalveolar lavage fluid (BALF). No significant difference was observed in body weight, differential cell counts, lactate dehydrogenase (LDH) and total protein in all solvent groups compared to saline by 28 days except 50% ethanol. However, myeloperoxidase (MPO) and macrophage inflammatory protein-2 (MIP-2) showed significant increase in 2% and 10% DMSO, 10% ethanol, 0.1% and 2% PEG-400, and 1% labrasol by longer dosing. All solvents except for 10% ethanol and 2% PEG-400 are suitable for agent aspiration.