LIPOSOMES: NOVEL DRUG DELIVERY CARRIER

MATERIALS USED FOR LIPOSOMES^{2, 5, 7, 8}
1.      Membrane forming components
Phospholipids that are the major components of the biological membranes are the building blocks of the liposomes. The phospholipids have tubular shape owning to the presence of two acyl chains attached to a polar head and on hydration, results into a bilayered membrane. Two types of phospholipids are there i.e. phosphodiglycerides and sphingolipids along with their corresponding hydrolysis products.
Classification of phospholipids
a.      Neutral phospholipids e.g. Sphingomyelin, Phosphatidylethanolamine and Phosphatidylcholine.
b.      Negatively charged phospholipids e.g. Dipalmitoyl phosphatidylcholine, Dipalmitoyl phosphatidyl acid (DDPA), Distearoyl phosphatidyl choline (DSPC), Dioleoyl phosphatidyl choline (DOPC) etc.
c.       Positively charged phospholipids e.g. 1, 2-dihexadecyl-N, N-dimethyl–N-trimethyl amine methyl ethanol amine etc.

2.      Membrane Additives (Sterols)
Cholesterol is the most commonly used sterol, which is included in the liposomal membranes. It has been called as the ‘motar’ of bilayers because by virtue of its molecular shape and solubility properties, it fills in empty spaces among the phospholipid molecules, anchoring them more strongly into the structure. Cholesterol is an amphipathic molecule and inserts itself into the membrane with its hydroxyl groups oriented towards the aqueous phase and aliphatic chain aligned parallel to acyl chains of the phospholipid molecules. In other words, cholesterol increases the transition temperature of the system by making the membrane more ordered. Cholesterol reduces this type of interaction to a great extent and provides both physical and biological stability.

3.      Charge inducers and Steric stabilizers
Stearylamine, dicetylphosphate, solulan C-24 and diacylglycerol are commonly used to impart either a negative or a positive surface charge. Since it is a well-known fact that negatively charged and positively charged liposomes are more rapidly uptaken by the reticulo-endothelial system as compared to neutral liposomes, charge inducers are used to overcome this problem. Also they proved to be useful in reducing aggregation as neutral liposomes show higher tendency to undergo aggregation.

4.      Other substances
In case, the drug is very prone to oxidation, antioxidants e.g. tocopherol, butylated hydroxy toluene and stabilizers are used. The use of preservatives is very common to increase the shelf-life of liposomal formulations.

MECHANISM OF TRANSPORTATION THROUGH LIPOSOMES^{2, 5}
Liposome can interact with cells by four different mechanisms:
1.      Endocytosis by phagocytic cells of the reticulo endothelial system such as macrophages and neutrophils.
2.      Adsorption to the cell surface either by nonspecific weak hydrophobic or electrostatic forces or by specific interactions with cell-surface components.
3.      Fusion with the plasma cell membrane by insertion of the lipid bilayer of the liposome into the plasma membrane, with simultaneous release of liposomal content into the cytoplasm
4.      Transfer of liposomal lipids to cellular or subcellular membranes, or vice versa, without any association of the liposome contents. It often is difficult to determine what mechanism is operative and more than one may operate at the same time.

CLASSIFICATION^{5, 6, 7}

1.      Based on composition and mode of drug delivery
A.    Conventional liposomes
These types of liposomes arecomposed of neutral or negatively charged phospholipids and cholesterol. It is useful for E.E.S targeting; rapid and saturable uptake by R.E.S; short circulation half life, dose dependent pharmacokinetics.

B.     pH sensitive liposomes
These types of liposomes arecomposed of phospholipids such as phosphatidyl ethanolamine, dioleoyl phosphatidyl ethanolamine. These are subjected to coated pit endocytosis at low pH, fuse with cell or endosomes membrane and release their contents in cytoplasm; suitable for intra cellular delivery of weak base and macromolecules. Biodistribution and pharmacokinetics are similar to conventional liposomes.

C.    Cationic Liposomes
These types of liposomes arecomposed of cationic lipids. These are mainly suitable for delivery of negatively charged macromolecules (DNA, RNA); ease of formation, structurally unstable; toxic at high dose, mainly restricted to local administration

D.    Temperature or heat sensitive liposomes
These types of liposomes arecomposed of dipalmitoyl phosphotidyl choline. These are vesicles showed maximum release at 41?C, the phase transition temperature of dipalmitoyl phosphotidyl choline. Liposomes release the entrapped content at the target cell surface upon a brief heating to the phase transition temperature of the liposome membrane.

E.     Immuno liposomes
These are conventional or stealth liposomes with attached antibody or recognition sequence. These are subjected to receptor mediated endocytosis. It has cell specific binding (targeting) and can release contents extra cellularly near the target tissue and drugs diffuse through plasma membrane to produce their effects.

F.     Long circulating or stealth liposomes
These types of liposomes arecomposed of neutral high transition temperature lipid, cholesterol and 5-10% of PEG-DSPE. These are subjected to hydrophilic surface coating, low opsonisation and thus low rate of uptake by R.E.S. So, it has long circulating half life (40 hrs) and dose independent Pharmacokinetics.

G.    Magnetic Liposomes
These types of liposomes arecomposed of phosphotidyl choline, cholesterol and small amount of a linear chain aldehyde and colloidal particles of magnetic iron oxide. These are liposomes that indigenously contain binding sites for attaching other molecules like antibodies on their exterior surface. These can be made use by an external vibrating magnetic field on their deliberate, on site, rapture and immediate release of their components.

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