Binding of Imipramine, Dosulepin, and Opipramol to Liposomes for Overdose Treatment

Polymer shielded liposomes were investigated as detoxifying agents for the weak bases imipramine and dosulepin and the diprotic drug opipramol. In vitro binding measurements in the presence of human serum samples revealed that the liposomes reduced the free drug concentration of the weak bases (corrected for protein binding) by 88-93%. The reduction for opipramol was around 76%. The results demonstrate that polymer shielded liposomes composed of anionic lipids are widely useful for drug overdose treatment. Polyethylene glycol chain lengths of 2000 and 5000 for the polymer coatings were also explored, and chain length showed no evidence of affecting drug uptake by liposomes. Liposomes compete favorably with other binding targets for drugs, and pharmacokinetic considerations suggest that liposomes could reduce toxicity by transporting drugs from fast-equilibrating organs such as the heart to slow-equilibrating organs such as the fat, muscle, and skin. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:3718-3729, 2009