*4.5. Liposome Formulation and Modifications*

In addition to classification by the origin of the target molecule, work in this area can be viewed based on the liposome formulation and molecular structure of the target molecule. Forster et al., in their initial work using IV liposomes, undertook initial in vitro work to evaluate which formulation had the greatest binding capacity to bind diltiazem in suspensions of fetal bovine serum. Both intravenous lipid emulsion and anionic dipalmitoylphosphatidylcholine (DPPC) liposomes entrapped diltiazem, a lipophilic weak base. Diltiazem uptake by DPPC liposomes increased by a factor of 14 as the pH of the aqueous centre dropped from 7.4 to 2, which is consistent with the principle of ion trapping [5]. This in vitro finding, subsequently replicated for other lipophilic weak bases [11], has translated into positive in vivo experimental results using pH-gradient liposomes for ammonia, verapamil and other molecules.

Target molecules with different molecular structure have been sequestered in dialysate via electrostatic and lipophilic interactions in the liposome membrane. The in vitro refinements of liposome structure to sequester PBUTs using cationic phospholipid and linoleic acid to displace PBUTs from albumin are yet to translate to in vivo findings.
