Direct Experimental Comparison of Liposome Formulation Processes for Poorly Permeable Solutes: Effect of Driving Force and Bilayer Disruption Mechanism

Liposomes can act as drug carriers because of their ability to encapsulate both hydrophilic and lipophilic substances, protect them from external factors, and facilitate controlled drug delivery or release. However, the physical properties and encapsulation efficiencies are strongly influenced by the choice of the liposome formation and the solute loading process. During liposome assembly, poorly permeable solutes can be rejected by the phospholipid membrane, resulting in a poor encapsulation efficiency. In this study, five different liposome formulation process routes have been directly experimentally compared: the heating method with sonication, the lipid film hydration method with either extrusion or sonication, and the freeze-thawing method applied to either preloaded or blank liposomes. 5(6)-Carboxyfluorescein and D-(+)-glucose were used as model solutes with different permeability and hydrophilicity profiles to assess the encapsulation efficiency and concentration retention factor of each formulation process route. The film hydration method followed by extrusion was found to be the most effective for carboxyfluorescein as a more permeable solute. In contrast, the film hydration method followed by sonication was found to be a more effective process for glucose, which is less permeable. The quantity of encapsulated solute per mass of lipids was found to increase with an increasing solute concentration in the loading solution, indicating a clear dependence on the concentration driving force.