Some Limits of Biocompatibility Testing for Lipophilic Leachates

Abstract

Medical device standards recommend using both a polar and non-polar solvent to extract materials prior to in vitro testing. Testing lipophilic extract in cell culture systems is limited by the toxicity of the lipophilic solvents used in extraction. Use of agar overlay and direct contact methods do not directly address the problem of testing for highly lipophilic leachates from device or material extracts. This particular problem was approached by 1) use of hydrotropes, and 2) by sealing the suspended cells in dialysis tubing and placing it directly in oil or media. The use of hydrotropes to eliminate micelle formation and increase the solubility of lipophilic compounds was not useful as the hydrotropes themselves were toxic to the cells at concentrations that significantly increased analyte solubility. Diffusion of hydrophobic compounds from either peanut oil or cell culture media into the dialysis tubing where the test cells in media reside was significantly higher for the cell culture media than the peanut oil. There were significant differences in toxicity for cells in dialysis tubing from devices extracted between peanut oil and media. This study illustrates the importance of examining if cell toxicity due to micelle formation versus that of soluble chemicals for lipophilic extracts.

Keywords

• Lipophilic
• biocompatibility
• medical device extracts