Liposomes Dr. Aws Alshamsan Department of Pharmaceutics Office: AA87 Tel:

Liposomes Spherical vesicles whose walls consist of hydrated bilayers of phospholipids

Phospholipids Polar Head Groups Three carbon glycerol

Phosphatidylcholines

Cholesterol

Liposomes Preparation

Liposomal structures SUV: Small unilamellar vesicle LUV: Large unilamellar vesicle MLV: Multilamellar vesicle

Liposome size Unilamellar liposomes are vesicles enclosed by a 6 to 7 nm thick single phospholipid bilayer. They range in size from 20 to 1000 nm according to the method of preparation. The small unilamellar vesicle [SUV] size range is μm, the large unilamellar vesicles [LUV] size range is greater than 0.06 μm.

Liposome size Multilamellar liposomes consist of concentric phospholipid bilayers separated by aqueous layers of 2.8 nm thickness. The multilamellar vesicle [MLV] size range is 0.1 – 0.5 µm

Drug loading

1.Encapsulation: The physicochemical properties of the drug itself, especially solubility and partition coefficient, are important determinant of the extent of its incorporation in liposomes. It is useful for water- soluble drugs, the encapsulation is simple hydration of a lipid with an aqueous solution of drug. The formation of liposomes passively entraps dissolved drug in the interlamellar spaces, essentially encapsulating a small volume.

Drug loading 2. Partitioning: A drug substance that is soluble in organic solvents will go through partitioning. It is dissolve along with phospholipid in a suitable organic solvent. This combination is dried first after that added directly to the aqueous phase and solvent residues remove under vacuum. The acyl chains of the phospholipids provide a solubilizing environment for the drug molecule. This will be located in the intrabilayer space.

Drug loading 3. Reverse loading: The reverse-loading mechanism uses for certain drugs may exist in both charged and uncharged forms depending on the pH of the environment. This type of drug can be added to an aqueous phase in the uncharged state to permeate into liposomes through their lipid bilayers. Then the internal pH of the liposome is adjusted to create a charge on the drug molecules. Once, charged the drug molecules no longer is lipophilic enough to pass through the lipid bilayer and return to the external medium.

Liposome classes

PEG-Liposomes

20 PEG-Liposomes Easily uptaken by macrophages Overcome by Stealth property (PEGylation)

Phosphatidylethanolamine

Immunoliposomes

Advantages of Liposomes 1. Liposomes are biocompatible, completely biodegradable, non-toxic, flexible and nonimmunogenic for systemic and non-systemic administrations. 2. Liposomes supply both a lipophilic environment and aqueous “milieu interne” in one system and are therefore suitable for delivery of hydrophobic, amphipathic and hydrophilic drugs and agents.

Advantages of Liposomes 3. Liposomes have the ability to protect their encapsulated drug from the external environment and to act as sustained release depots. 4. Liposomes can be formulated as a suspension, as an aerosol, or in a semisolid form such as gel, cream and lotion, as a dry vesicular powder for reconstitution or they can be administered through most routes of administration including ocular, pulmonary, nasal, oral, intramuscular, subcutaneous, topical and intravenous.

Advantages of Liposomes 5. Liposomes could encapsulate not only small molecules but also macromolecules DNA and proteins. 6. Liposomes are reduced toxicity and increased stability of entrapped drug via encapsulation. 7. Liposomes are increased efficacy and therapeutic index of drugs.

Advantages of Liposomes 8. Liposomes help to reduce exposure of sensitive tissues to toxic drugs. 9. Alter the pharmacokinetic property of drugs (reduced elimination, increased circulation life time) 10. Flexibility to couple with site-specific ligands to achieve active targeting.

Disadvantages of Liposomes 1. Production cost is high 2. Leakage and fusion of encapsulated drug / molecules. 3. Sometimes phospholipid undergoes oxidation and hydrolysis reaction 4. Short half-life 5. Low solubility 6. Instability

Evolution of liposomes

Liposomes interaction with cells

Hand-foot syndrome Palmar-plantar erythrodysesthesia (PPE), also called hand-to-foot syndrome