Pharmaceutical Manufacturing Handbook: Production and

446 LIPOSOMES AND DRUG DELIVERY
Conventional PEGylated or
Longcirculating
Phospholipid
PEGlipid
Cationic lipid
Helper lipid
Targeted or
immunoliposomes
Cationic
Antibody or
targeting ligand
FIGURE 1 Liposome types. Conventional liposomes are composed of phospholipids that
form bilayers enclosing an aqueous compartment. Cholesterol may be included in the bilayer
to increase membrane rigidity. Hydrophilic drugs can be encapsulated in the aqueous interior
of the vesicles and lipophilic drugs can be included in their membranes. Pegylated or long -
circulating liposomes have a surface coating of polyethylene glycol (PEG) molecules that
permits liposomes to escape opsonization (coating with plasma proteins — opsonins — that
make liposomes visible by RES macrophages). PEG - conjugated lipids are used for the preparation
of this type of vesicle. Targeted liposomes or immunoliposomes are liposomes that in
addition to a PEG coating (in most cases) have targeting moiety on their surface that directs
them to the preferred target. This targeting moiety may be a sugar (i.e., galactose, to target
cells with galactose receptors on their membranes) or other type of molecule or an antibody
(usually monoclonal antibody), in which case the liposomes are characterized as immunoliposomes.
Cationic liposomes are vesicles that consist of positively charged lipids (cationic
lipids) which may form complexes with negatively charged DNA molecules and thus are used
for gene delivery or targeting applications. For their preparation an additional lipid (helper
lipid) is usually required. Cationic liposomes can also have PEG molecules on their surface
(for longer circulation in the bloodstream) and/or targeting moieties. The last type of liposome
is the so called transformable liposome or elastic liposome . ( structure is presented and
explained in Figure 10 ).
charge of the lipids that can be positively or negatively charged, zwitterionic, or
noncharged. During liposome formation, these molecules arrange themselves by
exposing their polar parts toward the water phase, while the hydrocarbon moieties
(hydrophobic) adhere together in the bilayer. Two classes of lipids are mainly used
for liposome preparation: double - chain polar lipids and sterols (mainly cholesterol).
Such lipids form bilayers, in contrast to single - chain lipids (e.g., short - chain
phosphatidylcholine) that form micelles, upon their dispersion in water. [14] .
Double - chain lipids are either naturally occurring or synthesized in the laboratory.
They consist of glycerol or sphingosine and a polar head containing a phosphor -
or glyco - group. Glycerophopsholipids or phospholipids are the most popular, among
the other lipids, for the preparation of liposomal dispersions [15] . Phosphatidylcho-