The formation of
liposomes and their application as delivery systems for
injectable drugs are described.
Liposomes are microscopic vesicles composed of one or more
lipid membranes surrounding discrete aqueous compartments. These vesicles can encapsulate water-soluble drugs in their aqueous spaces and
lipid-soluble drugs within the membrane itself.
Liposomes release their contents by interacting with cells in one of four ways: adsorption, endocytosis,
lipid exchange, or fusion.
Liposome-entrapped drugs are distributed within the body much differently than free drugs; when administered intravenously to healthy animals and humans, most of the injected vesicles accumulate in the liver, spleen, lungs, bone marrow, and lymph nodes.
Liposomes also accumulate preferentially at the sites of
inflammation and
infection and in some solid
tumors; however, the reason for this accumulation is not clear. Four major factors influence
liposomes' in vivo behavior and biodistribution: (1)
liposomes tend to leak if
cholesterol is not included in the vesicle membrane, (2) small
liposomes are cleared more slowly than large
liposomes, (3) the half-life of a
liposome increases as the
lipid dose increases, and (4) charged liposomal systems are cleared more rapidly than uncharged systems. The most advanced application of
liposome-based
therapy is in the treatment of systemic
fungal infections, especially with
amphotericin B.
Liposomes are also under investigation for treatment of neoplastic disorders.
Liposomes' uses in
cancer therapy include encapsulation of known
antineoplastic agents such as
doxorubicin and
methotrexate, delivery of immune modulators such as N-acetylmuramyl-
L-alanine-D-
isoglutamine, and encapsulation of new chemical entities that are synthesized with lipophilic segments tailored for insertion into
lipid bilayers. Liposomal formulations of
injectable antimicrobial agents and
antineoplastic agents already are undergoing clinical testing, and most probably will receive approval for marketing in the early 1990s. Liposomal encapsulation of drugs represents a new drug delivery system that appears to offer important therapeutic advantages over existing methods of
drug delivery.