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SOM 3 > Liposomes > Flashcards

Liposomes Flashcards

1
Q

what are liposomes used for in pharmacy?

A

drug deliver systems

act as a vehicle/carrier component of nanomedicines

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2
Q

what type of material are liposomes?

A

natural or synthetic materials – polymers, proteins, lipid

in the nm range

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3
Q

what are the physical properties of liposomes?

A

hollow, or have a porous or solid interior

Closed, spherical vesicles of single or multiple lipid bilayers (lamellae), enclosing an internal aqueous core

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4
Q

how can liposomes be used to deliver drugs?

A

incorporated inside particles (encapsulation, entrapment)

on particle surfaces (adsorption, attachment)

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5
Q

why are drug delivery systems used?

A

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

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6
Q

how does sa:volume ratio affect degradation?

A

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

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7
Q

why is targeted drug delivery useful?

A

increased delivery efficacy and decreases the drug toxicity/side effects

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8
Q

why is chitosan nanoparticles important?

A

increase adhesion to mucosa and as a result, increase the retention time.

this allows drug transport across biological barriers (e.g. chitosan nanoparticles nasally)

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9
Q

what is preferred natural or synthetic liposomes?

A

synthetic as we can control the structure and purity

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10
Q

what are some examples of synthetic lipids?

A

phospholipids

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11
Q

what does it mean by phospholipid molecules are amphiphilic?

A

They contain a hydrophobic and a hydrophilic component

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12
Q

what can happen to hydrophobic heads in phospholipids?

A

they can have a surface charge

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13
Q

what happens to phospholipids in aq environments?

A

arrange themselves into bilayer structures → liposome formation (with energy input)

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14
Q

how can we classify liposomes?

A

size or by surface charge (cationic/anionic/neutral)

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15
Q

what size classification of liposomes are used the most? and why?

A

SUV - due to mainly being reproducible in manufactoring

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16
Q

how are liposomes prepared?

A

Lipid film hydration – very popular for lab-scale production (MAIN WAY)
* Solvent injection
* Reverse phase evaporation
* Microfluidic techniques

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17
Q

what organic solvents are used in lipid film hydration?

A

chloroform/methanol

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18
Q

explain lipid film hydration

A
  1. lipid is dissolved in an organic solvent
  2. flask is shaken/rotated in an rotary evaporation set up
  3. the organic solvent evaporates
  4. aqueous solution (buffer) added for hydration allowing the film to swell and form a bilayer
  5. stirring (T° > Tm)
  6. size reduction
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19
Q

why is the solvent and liposomes shaken/rotated during the heating phase?

A

due to the solvent being volatile

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20
Q

what are the different size reduction techniques?

A
  • extrusion (mainly used)
  • probe sonication
  • bath sonication
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21
Q

explain the extrusion process

A

filtered unit with an ideal pore size chosen
pressure and heat used to force the solution through the filter = uniform size

22
Q

what is phase transition temperature ?

A

Tm or Tc
Temperature at which lipids undergo a change in physical state from ordered gel phase to disordered liquid crystalline phase

23
Q

what happens to the liposomes if T° < Tm

A

they will be ordered
in a gel phase

24
Q

what happens to the liposomes if T° > Tm

A

they will be disordered
in a liquid crystalline phase

25
Q

what influences Tm?

A

Degree of saturation/unsaturation
and chain length

26
Q

how does Degree of saturation/unsaturation affect Tm?

A

increase the degree of unsaturation (increase C=C bonds) causing a kink in the chain, this required less energy to break apart = LOWERING Tm

27
Q

how does chain length affect Tm?

A

increase chain length = more hydrophobic interactions = larger amount of energy required to disorder the tails = HIGHER Tm

28
Q

what might liquid crystalline phase do?

A

lead to liposome instability, drug leakage

29
Q

why is cholesterol used in drug delivery?

A

inserting in liposomes = rigid tails = reduces bilayer permeability & increases drug retention

can abolish the Tm (at certain concentrations)

30
Q

how is liposomes size measured? and explain

A

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

31
Q

what measurements are given from DLS machines?

A

mean/average size of liposomes
particle size distribution (PDI %) of liposomes

32
Q

what is an ideal PDI?

A

ranges from 0-1

higher values = polydispersed sample, broad size distribution

therefore 0% is ideal

33
Q

how can liposome surface charge be measured?

A

electrophoretic mobility
Magnitude of zeta potential = indicator of particle stability

34
Q

what happens if your particle has a large zeta potential (±30 mV)?

A

tend to repel = prevent aggregation

35
Q

how do you calculate drug loading?

A
36
Q

how do you calculate entrapment efficacy

A
37
Q

how do liposomes deliver hydrophilic/hydrophobic/lipophilic/amphiphilic API’s?

A

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

38
Q

how can you tailor liposomes to have a more rigid membrane?

A

high Tm - saturated and high chain length
addition of cholesterol

39
Q

how can liposomes decrease aggregation? why is this important ?

A

using charged lipids, increases the stability

40
Q

what is PEG?

A

polyethylene glycol, family of hydrophilic polymers

Provides a hydrophilic coating on liposome surfaces

inhibits opsonisation by the coating

41
Q

what are opsonins?

A

blood-circulating components e.g. immunoglobulins, complement proteins

42
Q

what is opsonisation?

A

opsonins Bind to foreign particles in the blood and tag them for removal by phagocytic cells

43
Q

what are opsonised particles phagocytosed by?

A

macrophages of the MPS - mononuclear phagocyte system

44
Q

how can we avoid opsonisation?

A
45
Q

what are the outcomes from PEGylated molecules?

A

prolonged systemic circulation

facilitates liposome accumulation at tumour sites via EPR effect

46
Q

what is the EPR effect?

A

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

47
Q

what are MVLs? and why are they used?

A

multivesicular liposomes; release drugs over hours-weeks as lipid membrane erods/reorganises slowly = sustained drug release

48
Q

what are some examples of liposome adjuvants? and why are they used?

A

vaccines (e.g. shingles) due to their long lasting immunity obtained, providing cross protection

49
Q

what are virosomes? and why are they used?

A

liposomal bilayers formed from phospholipid + viral antigen components = enhanced antigen delivery

50
Q

what a lipid nanoparticles (LNPs)? and what are some examples of it?

A

liposomes but not arranged within a bilayer

examples; COVID-19 vaccines

51
Q

describe LNP formation

A

SOM 3 (26 decks)

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