Liposomes

What family are liposomes from?

-part of nanomedicines

How big are nanoparticles?

-1-100nm

What type of drug delivery are nanoparticles used for?

-parenteral drug delivery
-oral drug delivery
-ocular drug delivery
-pulmonary drug delivery

What are advantages of nanoparticles?

-size and surface characteristics can be easily manipulated
-made to control and sustain release of the drug during transportation as well as the location of the release
-more specific drug targeting and delivery
-reduction in toxicity while maintaining therapeutic effects

What are liposomes?

-microscopic spheres made from fatty materials: phospholipids and cholesterol

How are liposomes formed?

-as a result of self assembly of phospholipids in an aqueous media resulting in closed bilayered structures

What is the difference between micelle and liposome?

-micelles have a single lipid chain while liposomes have a lipid bilayer

What are the two cavities in a liposome and where to do put hydrophilic and hydrophobic drugs?

-hydrophobic cavity: hydrophobic drug in here; can disrupt liposome at high concentrations
-polar cavity: hydrophilic drugs go here; slowly released with high loading
-amphipathic drugs rapidly partition between both

What are the different classifications of liposomes?

-based on size
-based on method of preparation
-based on composition and in vivo application

What are classifications based on size?

-small unilamellar vesicles: ideal
-medium sized unilamellar vesicles
-large unillamellar vesicles
-oligolamellar vesicles
-multilamellar large vesicles
-multivescular vesciles

What are the different classifications based on method of preparation?

-vesicles prepared by lipid hydration followed by extrusion method*
-prepared by french press
-prepared by fusion
-prepared by reverse phase evaporation

What is the process of hydration method using extrusion?

What are the classifications based on the specific properties?

-conventional liposomes
-long circulating liposomes (stealth liposomes)

What is the major problem with liposomes? What are stealth liposomes?

-when liposomes are delivered by injection into the blood, there is the specific uptake of liposomes by reticuloendothelial system (RES)
-liposomes with PEG avoid the uptake by RES

What are targeted liposomes?

-combine passive targeted delivery (properties of long-circulating stealth liposomes) with an active targeting system

What are cationic liposomes?

-positively charged lipids used in gene therapy due to their interactions with negatively charged DNA

What are the advantages of liposomes?

-suitable for delivery of hydrophobic, hydrophilic, and amphipathic drugs and agents
-biocompatible and biodegradable
-suitable for controlled release
-delayed release: protect from degradation
-increases target site action via passive and active targeting
-suitable to administer via various routes

What are materials used in preparation of liposomes?

-phospholipids
-synthetic phospholipids
-cholesterol
and more

What is the strucutre of phospholipid?

-hydrophilic head and hydrophobic tail
-amphipathic

DIfference between lipids and phospholipids? (?)

-lipids are entirely hydrophobic

How do phospholipids with no unsaturated fatty acids fit together (no double bonds)?

-tightly because the fatty acid chains are parallel to each other

How do lipids with one or more unsaturated fatty acids fit together (has double bonds)?

-do not fit as tightly bc cis double bonds cause bends in the chains, which interfere with packaging

What tells you the lipid membrane fluidity?

-transition temperature (Tc)

What is transition temperature (Tc)? How do you measure this?

-temp at which the transition from a crystalline gel-like phase to a liquid crystalline phase occurs
-DSC

When does Tc increase? Decrease?

-increases as chain length of fatty chains increase
-decreases as chain length of fatty acids decrease and with the number of double bonds
-add double bonds=lowers Tc

Whatis the most common phospholipid?

-phosphatidylcholine

Why is cholesterol in the liposomes?

-gives rigidity to the membrane
-orients itself in the lipid layer so the OH group is close to the head group of the phospholipid so it can hydrogen bond

How does cholesterol affect the Tc?

-don’t need to worry about the Tc as much
-disrupter of the effects of the fatty acid chains
-below Tc- makes phospholipid more fluid
-above Tc- makes it more rigid

What are issues to consider when selecting lipids for liposomes?

-phase transition temp
-stability
-charge
-lipid mixtures
-cholesterol
-source

How do you measure the liposomes size?

-DLS: dynamic light scattering
-used for measuring particle size and particle size distribution for spherical nanoparticles
-requires material to be dispersed in a solvent and that all nanoparticles exist individually

What does the DLS specifically measure?

-the brownian motion: random movement of particles due to the bombardment by the solvent molecules surrounding them
-large the particle=slower the motion

What is the hydrodynamic diameter?

-value refers to how a particle diffuses within a fluid

Why do you want zeta potential to be away from 0?

-shows that it is stable

How do you visualize liposomes?

-TEM

What other things do you need to test in terms of liposomes?

-stability and encapsulation efficiency

What is the evolution of liposomes?

-conventional (non-targeting) → first gen stealth liposome (passive targeting) → second gen (ligand-targeting)

How are liposomes used in cancer therapy?

-improve pharmacological properties of many agents

Limitations of liposomes?

-rly expensive
-short shelf life
-physical and chemical instability
-limited encapsulation
-possibility of new side effects
-efficacy