Ameninta Cesanina Singarimbun

1506725262 – Teknik Kimia

LTM 2-CDR
LIPOSOMES IN DRUG DELIVERY

Liposomes : Brief Overview of Preparation and Properties

 Liposomes are artificial vesicles that have been investigates and dicussed multiple times.
To increase liposome membrane stability and slow down their disintegration and release
of incorporated drugs, various amounts of cholesterol are incorporated into the liposomal
membrane.
 Liposomes are in general biocompatible, cause no or very little antigenic, pyrogenic,
allergic, and toxic reactions (unless contain impurities or contaminations), easily undergo
biodegradation, protect the host from any undesirable effects of the encapsulated drug, and
protect an entrapped drug from premature inactivation by the physiological medium.

Liposomes In Vivo
 Liposomes are eliminated from the blood by the cells of the MPS primarily in the liver.
Liposomes of larger size are captured by MPS organs faster. Antibodies and their
fragments, which are the most widely used targeting moieties for liposomes, can be
attached to liposomes without affecting liposomes’ integrity or antibody properties, by
covalent binding to the liposome surface or by the insertion into the liposomal membrane
upon premodification with hydrophobic residues.
- Long-circulating liposomes : Liposomes are capable of accumulating in various
pathological areas with compromised vasculature. To enhance the circulation of liposomes
(longer circulation for certain target) different method have been suggested. One of the
idea that have been suggested was PEGyltaed liposomes which already proved to be
adaptable to various area.
- Targeting of Long-circulating liposomes : advanced technologies for the preparation of
targeted long-circulating liposomes are used, and the targeting moiety is usually attached
above the protecting polymer layer, to minimize the steric hindrances for the interaction
with the target, by coupling it with the distal water-exposed terminus of a liposome-grafted
polymer molecule.

Administration Routes for Liposome-Based Preparations

 Liposomes as a dosage form allow for a broad variety of administration routes, each having
its own limitations.
- GM 1 and GM type III : survive in GI tract
- PEG Coated : for oral delivery
- Ovalbumin in PEG-coated : Muscosal immune response.
- Aerosolized Liposomal : Lung delivery
 Liposomes were found to increase skin penetration of many hydrophilic substances.
Deformable liposomes have also been used for skin delivery of ketotifen. The combination
of liposomes and iontophoresis for transdermal delivery also yielded promising results.
Liposomes have been used for lymphatic delivery of methotrexate and for magnetic
 resonance imaging, using gadolinium (Gd) loaded liposomes. An interesting example of a
new approach is a combination of radiofrequency tumor ablation with intravenous
liposomal doxorubicin, which resulted in better tumor accumulation of liposomes and
increased necrosis in tumors.

A Special Case of Liposomal Peptide and Protein Drugs

 Proteins and peptides intended as
therapeutic agents often demonstrate
low biological stability. One of the
technologies to improve
pharmacological properties of
proteins and peptides is their
incorporation into liposomes
 The potential ability of liposome
encapsulated enzymes to enter the
cytoplasm or lysosomes of live cells
is of primary importance. for the treatment of inherited diseases caused by abnormal
functioning of some intracellular enzymes.

Liposomes as Vehicles for Delivery of DNA and Related Materials

 Although viral systems are currently the most common means for DNA delivery, non viral
systems have also been developed. Cationic lipid-based liposomes are easy to prepare,
reasonably cheap, and nonimmunogenic. Since many of the finer features of these delivery
systems and mechanisms remain insufficiently understood, recent studies in this popular
area concentrate on structure, function, structure–activity relationships, detailed
mechanisms of liposome mediated gene delivery, and improved efficiency of transfection.
 Polycationic liposomes for gene delivery have been suggested. It is a liposomes modified
by cetylated polyethylene imine, which anchors in the membrane via cetyl residues and
binds DNA via positive charges.
 Liposomes composed of ursodeoxycholic acid and cationic DOTAP effectively deliver
oligonucleotides into HaCaT cells. Combination of the proapoptotic peptide D-
(KLAKLAK)2 and Bcl-2 antisense oligo G3139 in a single liposomal preparation resulted
in a synergistic effect and improved cancer therapy in mice.

Liposomes as Immunological Adjuvants

 Liposomes are known to be effective immunological adjuvant for various antigens. They
are capable of inducing both humoral and cellular immune responses toward liposomal
antigens. Liposomes with encapsulated protein or peptide antigen are phagocytosed by
macrophages and eventually end up in lysosomes.

Liposomes in Medical Imaging

 Several different methods to label/load the liposome with a contrast/reporter group:
(a) Label is added to liposomes during the manufacturing process.
(b) Label is adsorbed onto the surface of preformed liposomes
(c) Label is incorporated into the lipid bilayer of preformed liposomes;
 (d) Label is loaded into preformed liposomes using membrane-incorporated transporters, ion
channels, or concentration gradients.

Clinical Applications :
1. Archaeosomes : Solvent extraction is main method for obtaining total lipids of
archaeobacteria. Archeobacteria membranes have diether and/or tetraether linkages that
are used for generation of lipid layers of archeosomes. The higher efficiency of
archeosomes in drug/gene delivery is resulted from the biocompatibility and higher
stability of these systems.
2. Niosomes : Preparation of liposomes by nonionic surfactants such as alkyl ethers or alkyl
esters results in niosome structures. An advantage of niosomes is storage and handling with
biodegradable, biocompatible and non-immunogenic properties without any specific
conditional requirements.
3. Novasomes : Novasomes are produced by mixture of polyoxyethylene fatty acids (as
monoester), free fatty acids and cholesterol.
4. Cryptosomes : Mononuclear phagocytic system (MPS) clears conventional liposomes from
RES. In order to limit such a drawback, polyethylene glycol (PEG) derivatives are suitable
choices. This type of liposome modification is called stealth liposome or cryptosome..
5. Emulsomes : These structures have properties of emulsion and liposomes.
6. Vesosomes : Vesosomes is a multi-compartmental structure of lipid vesicles, derived from
liposomes, which are potentially powerful models used to deliver drugs.

Daftar Pustaka
Siepmann, Juergen. etc. 2012. Fundamentals and Applications of Controlled Release Drug
Delivery. London. Springer