SL22107: Liposomes

What happens at low amphiphile concentration

The molecules disperse randomly with no order

What happens at high concentration of amphiphilic molecules

Surfactant concentration > CMC

Amphiphilic molecules spontaneously assemble into micelles or vesicles

Hiding the hydrophobic tail of the amphiphile

Describe the 2 transformative phases in micelles as amphiphile concentration increases

At high concentration micelles form hexagonal columnar phase/middle phase: amphiphiles form long cylinders

At higher concentration a lamellar/neat phase forms: amphiphiles seperated by thin layers of water

What is a liposome

A vesicular structure based on one or more lipid bilayer encapsulating an aqueous core

Amphipathic: hydrophilic head and 2 hydrophobic tails

A lipid crystal

How is a liposome formed

Phospholipid + water forms a phospholipid bilayer in neat phase

At a high concentration the bilayer self-assembles into spherical liposome with aqueous core and hydrophobic outer layer

Why do liposomes form lipid bilayers

Spontaneously orientate in water to give the most THERMODYNAMICALLY STABLE conformation

Hydrophilic head faces out

Lipid chains faces in

Multilamellar or unilamellar

Several bimolecular lipid lamellae separated by aqueous layers = multilamellar liposome

Single lipid lamellae formed by sonification of units = unilamellar liposome

What are the functions of liposomes

Can carry lipophilic drugs fully buried in lipid bilayer

Can carry hydrophilic drugs sequestered in aqueous interior of the liposome

Can carry drugs with intermediate logP partition between lipid and aqueous phases

Can carry water soluble and lipid soluble drugs

Examples of liposomal agents

Phosphatidylcholine

Phosphatidylethanolamine

Examples of liposome uses

• Sterols, glycolipids, organic acids and bases, hydrophilic polymers, antibodies

• Antimicrobial agents, chelating agents, peptides, proteins

What is the effect of alkyl chain lengths and unsaturation

Longer unsaturated hydrocarbon chains produce rigid bilayers with low permeability at room temperature

What is the effect of cholesterol

• Makes the bilayer rigid

• Makes the system more stable to retain the entrapped drug

Stable vs fluid bilayer systems

Stable systems can retain entrapped drugs for longer periods

Fluid bilayer systems are better for rapid release

What other factors can contribute to liposome stability

• Lipid composition

• Storage condition

• Light

• Oxygen

• Temperature

• Cholesterol

• Inert atmosphere

At what point do liposomes swell

Spontaneously swell in water above Tm

What are the advantages of liposomes

• Biocompatible/ biodegradable

• Composed of natural phospholipids: Biologically inert, weakly immunogenic, low intrinsic toxicity

• Good biodistribution around the body

• Good at targeting specific receptors

How can liposomes improve the circulation of drugs

• Altered toxicity profile of amphotericin B and Doxorubicin to make them less toxic to human cholesterol cells

• Longer circulation in the body which increases tumour deposition of liposomes associated agents

What are the 4 types of liposomes

Conventional: neutral/negative charge used for passive targeting to cells

Sterically stabilised: hydrophilic coating used for prolonged circulation times

Immunoliposomes: targets antibodies and delivery of anticancer drugs

Cationic liposomes: positively charged used for delivery of genetic material (DNA is negative)

What are the advantages of conventional liposomes

• Protect encapsulated molecules from degradation

• Can passively target tissues e.g. spleen, liver

• Rapidly taken up by mononuclear phagocyte systems

• Can be used for antigen delivery e.g. HEP A vaccine

How are MPS targeted by liposomes

Deliver antiparasitic and antimicrobial drugs

Encapsulates immunomodulators in activated macrophages in cancers

What are long circulating liposomes (LIPOSOME + PEG = steric hindrance = longer half life)

Liposomes covalently attached to hydrophilic polymer/ polyethylene glycol

Highly hydrated PEG group creates a steric barrier

Prevents interactions with molecular and cellular components in biological component (aka stops the body from attacking/metabolize the drug too quickly)

Increasing the half-life and serum concentration of the drug

What is the structure of immunoliposomes

Specific antibodies or antibody fragments on the surface to enhance target site binding

Where can PEG components couple to

to the surface

to the terminal ends

How does cationic liposomes deliver genetic material

• Positive lipid component neutralizes negatively charged DNA

• Causes DNA to condense into a compact structure

• Can form an aggregate or DNA surrounded by lipid bilayer

Describe which liposomes can induce toxicity/reaction

Cationic: activates complements inducing ADR

PEGylated liposomes: activates transient reaction