Liposomes Flashcards
What are liposomes?
Liposomes are spherical self-closed structures, composed of curved lipid bilayers, which enclose part of the surrounding solvent into their interior.
Liposomes are composed of amphiphilic lipids.
What is the mechanism of liposome formation?
The hydration of outer monolyer predominates compared to inner layers.
The hydrophilic group of phospholipid expands and forms “blisters”.
Aqueous phase permeate through the blisters and form bilayers, resulting in formation of tubular fibrils. This increases the surface area in contact with aqueous phase.
The exposure of the hydrophobic moieties in phospholipids to the aqueous environment is thermodynamically unfavourable. This will force the bilayers to round up and form multilamellar vesicles (MLVs).
How are drugs loaded in liposomes?
Hydrophilic drugs are entrapped in the central aqueous core and in the aqueous spaces between the successive bilayers of liposomes.
Hydrophobic drugs are entrapped in the hydrophobic region within the bilayers.
What are the advantages of drug entrapment (encapsulation) in liposomes?
Provision of sustained release formulation.
Targeted drug delivery.
Gene internalization.
Protection of entrapped material from metabolic degradation in vivo.
Solubilisation of hydrophobic materials.
What are the four proposed mechanisms for liposome-cell interactions?
Adsorption - liposome is asdorbed at the cell surface, followed by extracellular release of the liposome-entrapped drug, which may be taken up by the cell via passive or active transport systems.
Lipid exchange - lipophilic component of the liposome bilayers may be transferred to the cell membranes and released into the cytoplasm.
Endocytosis - the whole liposome is engulfed by cell into the lysosomes where liposomes are digested and their contents released.
Fusion - liposome fuses with cellular membrane or endosomal membrane, followed by intracellular release of liposome contents. For fusion to occur, liposomes should be functionalised with fusion proteins or peptides.
What is the type of mechanism dependent on?
Size of liposome.
Surface charge of liposome.
Bilayer composition of liposome.
Type of ligands attached to liposomes.
Type of cell and the cellular microenvironment around the cell.
How are liposomes cleared?
Liposomes are not excreted through renal clearance, due to their large size that hinders glomerular filtration.
Liposomes are cleared by the reticulo endothelial system (RES) and breakdown of the liposome structure.
Liposome clearance takes place mainly through liver and spleen, where macrophages are present.
Factors influencing liposomal drug clearance from blood circulation:
Liposome size.
Liposome surface properties.
Lipid phase composition.
What are stealth liposomes?
The new generations of long-circulating liposomes.
SSL are formulated from polyethylene glycol (PEG) derivatives of phospholipids (e.g. PEG-disteroyl phosphatidylethanolamine) to produce vesicles with more hydrophilic surfaces.
The hydrophilicity of the liposome surfaces would provide steric stabilisation by making bilayers hindered and thus more resistant to opsonisation and hence less detectable by the macrophages and less RES-mediated clearance.
Why are long-circulating liposomes used for anticancer drug delivery?
Liposomes which are coated with polyethylene glycol will have higher hydrophilicity of their surfaces and hence less opsonization and subsequently lower RES-mediated clearance.
This means longer circulation time of the liposomes (encapsulating the anticancer drug) and subsequently higher chances of liposome extravasation into tumour cells.
Tumours have enhanced permeability and retention (EPR) effect compared to normal tissues due to the impaired lymphatic drainage in tumors.
What factors influence delivery of anticancer liposomes to the tumor?
Formulation factors:
Liposome size.
Liposome surface charge.
Lipid composition of liposomes (e.g. presence of cholesterol, PEGylation, etc.).
Biological factors:
Activity of the RES.
Blood perfusion into the tumor tissues.
Vascular permeability at the tumor site.
