Liposomes Flashcards
what are liposomes used for in pharmacy?
drug deliver systems
act as a vehicle/carrier component of nanomedicines
what type of material are liposomes?
natural or synthetic materials – polymers, proteins, lipid
in the nm range
what are the physical properties of liposomes?
hollow, or have a porous or solid interior
Closed, spherical vesicles of single or multiple lipid bilayers (lamellae), enclosing an internal aqueous core
how can liposomes be used to deliver drugs?
incorporated inside particles (encapsulation, entrapment)
on particle surfaces (adsorption, attachment)
why are drug delivery systems used?
improve drug potency and efficacy by…
* Improving drug solubility and dissolution - Small carrier size, high surface area:volume ratio
* Providing a sustained/controlled drug release
* Prolonging drug residence time in the systemic circulation
* Protecting drug from harsh in vivo conditions - Most effective if drug is encapsulate
* Improving drug transport across biological barriers
* Facilitating targeted drug delivery- Enhanced delivery to particular/specific cells or tissues
how does sa:volume ratio affect degradation?
as its easier for aqueous fluid (e.g. GI fluid) to penetrate the particle via the polymer = faster drug release due to the molecule being subjected to degradation
why is targeted drug delivery useful?
increased delivery efficacy and decreases the drug toxicity/side effects
why is chitosan nanoparticles important?
increase adhesion to mucosa and as a result, increase the retention time.
this allows drug transport across biological barriers (e.g. chitosan nanoparticles nasally)
what is preferred natural or synthetic liposomes?
synthetic as we can control the structure and purity
what are some examples of synthetic lipids?
phospholipids
what does it mean by phospholipid molecules are amphiphilic?
They contain a hydrophobic and a hydrophilic component
what can happen to hydrophobic heads in phospholipids?
they can have a surface charge
what happens to phospholipids in aq environments?
arrange themselves into bilayer structures → liposome formation (with energy input)
how can we classify liposomes?
size or by surface charge (cationic/anionic/neutral)
what size classification of liposomes are used the most? and why?
SUV - due to mainly being reproducible in manufactoring
how are liposomes prepared?
Lipid film hydration – very popular for lab-scale production (MAIN WAY)
* Solvent injection
* Reverse phase evaporation
* Microfluidic techniques
what organic solvents are used in lipid film hydration?
chloroform/methanol
explain lipid film hydration
- lipid is dissolved in an organic solvent
- flask is shaken/rotated in an rotary evaporation set up
- the organic solvent evaporates
- aqueous solution (buffer) added for hydration allowing the film to swell and form a bilayer
- stirring (T° > Tm)
- size reduction
why is the solvent and liposomes shaken/rotated during the heating phase?
due to the solvent being volatile
what are the different size reduction techniques?
- extrusion (mainly used)
- probe sonication
- bath sonication
explain the extrusion process
filtered unit with an ideal pore size chosen
pressure and heat used to force the solution through the filter = uniform size
what is phase transition temperature ?
Tm or Tc
Temperature at which lipids undergo a change in physical state from ordered gel phase to disordered liquid crystalline phase
what happens to the liposomes if T° < Tm
they will be ordered
in a gel phase
what happens to the liposomes if T° > Tm
they will be disordered
in a liquid crystalline phase
what influences Tm?
Degree of saturation/unsaturation
and chain length
how does Degree of saturation/unsaturation affect Tm?
increase the degree of unsaturation (increase C=C bonds) causing a kink in the chain, this required less energy to break apart = LOWERING Tm
how does chain length affect Tm?
increase chain length = more hydrophobic interactions = larger amount of energy required to disorder the tails = HIGHER Tm
what might liquid crystalline phase do?
lead to liposome instability, drug leakage
why is cholesterol used in drug delivery?
inserting in liposomes = rigid tails = reduces bilayer permeability & increases drug retention
can abolish the Tm (at certain concentrations)
how is liposomes size measured? and explain
dynamic light scattering (DLS)
Intensity of scattered light (at a given angle) over time is measured
* Fluctuates due to Brownian motion and diffusion of particles
* Diffusion related to particle size
what measurements are given from DLS machines?
mean/average size of liposomes
particle size distribution (PDI %) of liposomes
what is an ideal PDI?
ranges from 0-1
higher values = polydispersed sample, broad size distribution
therefore 0% is ideal
how can liposome surface charge be measured?
electrophoretic mobility
Magnitude of zeta potential = indicator of particle stability
what happens if your particle has a large zeta potential (±30 mV)?
tend to repel = prevent aggregation
how do you calculate drug loading?
how do you calculate entrapment efficacy
how do liposomes deliver hydrophilic/hydrophobic/lipophilic/amphiphilic API’s?
Hydrophilic APIs can be incorporated within the aqueous core, inter-bilayer spaces
* Lipophilic/hydrophobic APIs can associate with lipid tails within bilayers
* Amphiphilic APIs can incorporate into both lipid bilayer and aqueous spaces
how can you tailor liposomes to have a more rigid membrane?
high Tm - saturated and high chain length
addition of cholesterol
how can liposomes decrease aggregation? why is this important ?
using charged lipids, increases the stability
what is PEG?
polyethylene glycol, family of hydrophilic polymers
Provides a hydrophilic coating on liposome surfaces
inhibits opsonisation by the coating
what are opsonins?
blood-circulating components e.g. immunoglobulins, complement proteins
what is opsonisation?
opsonins Bind to foreign particles in the blood and tag them for removal by phagocytic cells
what are opsonised particles phagocytosed by?
macrophages of the MPS - mononuclear phagocyte system
how can we avoid opsonisation?
what are the outcomes from PEGylated molecules?
prolonged systemic circulation
facilitates liposome accumulation at tumour sites via EPR effect
what is the EPR effect?
Enhanced permeability and retention effect
Disruption of endothelial barrier at inflammation sites, sites of tumour growth – leaky vasculature
* Liposomes can escape through gaps in leaky vasculature if ≤ 200 nm = selective accumulation of liposomes
what are MVLs? and why are they used?
multivesicular liposomes; release drugs over hours-weeks as lipid membrane erods/reorganises slowly = sustained drug release
what are some examples of liposome adjuvants? and why are they used?
vaccines (e.g. shingles) due to their long lasting immunity obtained, providing cross protection
what are virosomes? and why are they used?
liposomal bilayers formed from phospholipid + viral antigen components = enhanced antigen delivery
what a lipid nanoparticles (LNPs)? and what are some examples of it?
liposomes but not arranged within a bilayer
examples; COVID-19 vaccines
describe LNP formation
