Biomaterials for Drug Delivery Flashcards

1
Q

What is the definition of a drug delivery system

A

A formulation or device that enables the introduction of a therapeutic substance in the body and improves its efficacy and safety by controlling the rate, time and place of release in the body

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2
Q

What 3 divisions does drug delivery encompass?

A
  • The administration of the therapeutic product (IV, injection, tablet)
  • The transport of the active ingredient to the target tissue
  • The release rate of the active therapeutic ingredient
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3
Q

Name a few microparticle drug delivery systems

A
  • Micelles
  • Solid Lipid nanoparticles
  • Liposomes
  • Niosomes
  • Gold nanoparticles
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4
Q

Explain how nanoparticles effectively target cells and release their drug payload

A

1) NPs containing a drug payload are coated in specialised proteins and ligands to target specific cell receptors
2) The NPs bind to the target cells via membrane proteins
3) This binding triggers the cell to ingest the NP
4) Enzymatic ingestion of the NP causes the drug to be released

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5
Q

Name a few brain related disorders

A
  • ALS
  • Alzheimer’s
  • Stroke
  • Migraine
  • Vertigo
  • Lipid Storage Disease (LSD)
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6
Q

What is Alzheimer’s caused by?

A

The clustering of amyloidal Beta proteins in the brain

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7
Q

How can Alzheimer’s be treated using nanoparticles

A

Gold nanoparticles
- Gold nanoparticles modified to target specifically amyloidal beta proteins
- These gold NPs bind to the clustered proteins in the brain and are irradiated using microwaves
- This causes the NPs to heat up and destroy the proteins, dissipating the aggregate

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8
Q

How have cancerous brain tumours been treated using nanoparticles?

A

Ferromagnetic Nanoparticles
- Ferromagnetic nanoparticles (made of iron oxide in a CaO-SiO2 matrix) are injected into the target cancerous tissue
- An alternating electromagnetic field is fed through the target tissue causing the particles to heat up killing the cancer cells
- Cancerous cells are destroyed at 43 degrees while regular cells can withstand heats to 48 degrees

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9
Q

Explain how Micelles have been used to target brain disorders?

A

Micelles are considerably smaller than most micro and nano particles.
Therefore they are able to carry a drug payload across the BBB to specific target cells

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10
Q

List the different drug release profiles

A
  • Immediate (injection)
  • Delayed
  • Prolonged (microparticles)
  • Extended (same as prolonged)
  • Repeated (Capsules containing lots of microparticles)
  • Controlled (insulin pumps)
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11
Q

What are some considerations to evaluate when optimising drug delivery?

A
  • The drug release profile (how long and when)
  • The administration route to reach target tissue
  • The mechanism by which it releases
  • Reduction of Side effects
  • Patient Compliance
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12
Q

Give another example of a drug release mechanism that uses tungsten

A

Tungsten loaded hydrogels
- A calcium alginate microgel containing API and tungsten particles is administered
- Ultrasound waves are fed to the administration site. These waves cause the tungsten particles to vibrate, vibrating the microgel particles, mechanically shaking out the API

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13
Q

Explain how generic microgels offer a prolonged release profile

A

Microgels are hydrophilic hydrogel particles, which contain API embedded within their polymer mesh
When in contact with water the microgel absorbs it swelling and enabling the slow controlled release of drug

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14
Q

Explain how a prolonged release drug profile can be achieved through capsules and tablets

A
  • Adding additional layers to slow degradation
    Polymer coating the particles
    Adding diluent to slow absorption
    Changing concentration of particles in diluent
    Particle and tablet size
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15
Q

How can controlled release of drugs be acheived?

A

Through devices that continuously feed drugs to the body such as IV fluids, Insulin pumps or buccal pumps

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16
Q

Name some anatomical routes for drug delivery

A
  • Parenteral (avoiding digestion)
  • Rectal
  • Intra (fascia, venous, muscular)
  • Transdermal
  • Topical
  • Pulmonary
  • Trans nasal
17
Q

Name some advantages and disadvantages for oral drug delivery

A

+ Easy Administration
+ High patient compliance
- Doesn’t avoid first pass metabolism
- Some drugs irritate the GI tract

18
Q

Name some advantages and disadvantages for parenteral drug delivery

A

+ High bioavailability
+ Avoids first pass metabolism
+ Rapid delivery and action
- Invasive and painful
- Low patient compliance
- Complications arise due to invasive nature
- Easily can go over the safe effective concentration

19
Q

Name some advantages and disadvantages for nasal drug delivery

A

+ Direct delivery to brain through olfactory nerve
+ Precise drug targeting
+ Non-invasive
+ Fast drug action due to surrounding tissue and vasculature
- poor drug bioavailability due to mucocilary defence
- Can only delivery small drug dosages

20
Q

Why are drugs absorbed so effectively in the nasal cavity?

A

The olfactory epithelium has a rich vascular network, which enables rapid absorption straight into the blood stream

21
Q

How are drugs administered nasally able to get past the BBB?

A

The olfactory epithelium is in direct contact with the olfactory nerve which is in direct contact with the brain, so drugs that interact with this nerve have direct access to the CNS

22
Q

Describe the mechanism in the nasal space that defends against pathogens but also makes drug absorption harder

A

Mucociliary Clearance
This is a combined action of mucous producing goblet cells and cilia lined epithelial cells that line the respiratory tract
The mucous contains a protein called mucin that binds and traps inhaled particles, while cilia sweep the the mucus layer along the respiratory tract to swallow or cough out

23
Q

What 4 types of nanoparticles have engineers invented to overcome this line of defence in the nasal cavity called the mucociliary clearance

A

1) Mucus penetrating NPs
2) Mucoadhesive NPs
3) Olfactory Targeting NPs
4) NP with cell penetrating peptides

24
Q

Describe how Mucus penetrating NPs effectively delivery drugs

A

These NPs are coated in proteins that do not like to interact with mucin, like oil in water

24
Q

Describe how Mucoadhesive NPs effectively delivery drugs

A

These NPs are coated in proteins that are resistant to mucin prolonging the time NPs can have diffusing through the mucous layer before being degraded by the enzymes

24
Q

Describe how NPs with cell penetrating peptides delivery drugs

A

These NPs have specific amino acid chains on their surface that can penetrate the mucus layer directly targeting specific cells

24
Q

Describe how Olfactory targeting NPs effectively delivery drugs

A

These NPs are coated in ligands designed to precisely recognise target cells in the olfactory region, binding on the cell membrane and releasing their content

25
Q

Explain the process behind PLA, PLGA and PLG nanoparticle production (Double emulsion)

A

W/O/W Double Emulsion nanoparticle fabrication
1) Emulsify the dispersed aqueous drug solute phase with the continuous phase (polymer dissolved in acetone)
2) This creates the primary emulsion (W/O)
3) Emulsify the primary emulsion with another aqueous phase, homogenising the emulsion to get nanoparticles of uniform size
4) Evaporate the acetone, leaving polymer nanoparticles containing liquid drug
5) Freeze-dry the solution remove the water leaving polymer nanoparticles

26
Q

Explain the production process of creating VB loaded PCL nanoparticles

A

W/O/W Double Emulsion
1) Emulsify the aqueous drug phase with the continuous PCL dissolved in methylene chloride phase
2) This produces the primary W/O emulsion
3) Emulsify and homogenise the primary phase with another aqueous phase (surfactant and water)
4) Heat the double emulsion to evaporate the lipophilic solvent, leaving a PCL coat
5) Centrifuge the solution to homogenise the nanoparticles
6) Freeze-dry the solution to remove aqueous phase leaving PCL nanoparticles loaded with VB

27
Q

What are mucoadhesive polymeric nanoparticles

A

These are particles designed specifically to adhere to mucosal tissues, to provide an very specific drug delivery profile via controlled release mechanics

28
Q

How are the well known mucoadhesive chitosan nanoparticles created

A

TPP droplets are added to Chitosan dissolved in acetic acid while being stirred.
This forms crosslinks forming particles in the solution
The particles are homogenised and purified via filtration and centrifugation

29
Q

What is chitosan made from specifically?

A

The partial deacetylation of chitin.
It is a polysaccharide made from glucosamine units bonded by glycosidic bonds