The drug encapsulation efficiency, sterility, drug retention, preparation methods, and the feasibility of large-scale production depend on the selection of drug loading methods in liposomes, as well as the stability, cost, and effectiveness of liposomes. There are two different methods for adding drugs to liposomes, namely passive drug loading and active drug loading. In passive drug loading methods, drugs are encapsulated in liposomes during the preparation process. In active drug loading methods, drugs are loaded into intact liposomes (active loading).
(1) Passive drug loading technology: Whether to use passive drug loading technology depends on the ability of liposomes to encapsulate a specific volume of aqueous phase during formation, which contains dissolved drugs or solutes. For hydrophilic drugs, the encapsulation efficiency of passively loaded liposomes is related to the volume of the aqueous phase where the liposomes are located, and the properties of the liposomes themselves depend on the concentration of phospholipids in the dispersion system, the number of compartments, and the morphology of the liposomes. Lipophilic drugs interact with phospholipid bilayers, therefore, the encapsulation efficiency depends on the type and concentration of phospholipids. Morphological parameters do not affect drug encapsulation efficiency. Using passive drug delivery technology, water-soluble drugs are encapsulated in the aqueous phase of liposomes, while lipophilic drugs are encapsulated in the bilayer (lipid phase) of liposomes. The lipophilic portion of drugs or bioactive substances will be embedded between liposome phospholipids, while their water-soluble portion is located in the aqueous phase of liposomes, thus being encapsulated.
(2) Active drug loading technology: For the encapsulation of active drugs, the prepared blank liposomes are mixed with a concentrated drug solution, incubated for a period of time, and the drugs are evenly distributed in the liposomes through diffusion process. This method is better because the phospholipid bilayer has high permeability for drug diffusion, thus achieving a higher encapsulation efficiency at an appropriate time. Due to concentration gradient, drugs can penetrate into liposomes through lipid bilayers until equilibrium is reached between the surrounding medium and the interior of the liposomes. During active loading, water-soluble drugs interact with the polar head groups of phospholipids and cannot enter the interior of liposomes. The amount of hydrophobic drugs that can enter liposomes depends on the degree of spatial limitation of the lipid bilayer. For amphiphilic drugs, they are difficult to retain in liposomes as they can quickly penetrate the lipid bilayer. This method has many advantages, such as not adding active ingredients during the preparation of liposomes, so the safety precautions that must be taken when dealing with toxic drugs can be reduced to a lower level. The disadvantage of this method is that it only limits a small portion of drugs that exhibit weak alkaline or acidic properties, and can only penetrate the bilayer without charge, rather than under charge.
