Week 2 - Nanotechnology and Nanomedicines

Question 1

What are novel / new formulations for changing PK

Nanomedicines, drug conjugates

Answer 1

Nanomedicines are…
- Smaller size (< 100 nanometers)

• Release of drug depends on design
  - can be RAPID or CONTROLLED release
  - improved efficacy
• Enhanced targetteing
  - precise drug delivery by attaching molecules to surface of nanoparticle
• Improved tissue penetration
  - esp. in tumours
• Improved distribution
• High SA:Vol ratio
  - increased interactions with surroundings

Drug Conjugates:
- mAbs are examples of conjugates
- advantages = all above AND reduced systemic toxicity, prolonged cirulation time

Question 2

What are the effects of PEGylation

Answer 2

Adding polyethyl glycol (PEG) to nanoparticle IMPROVES the drug STABILITY and BIOAVAILABILITY

PEG is added to surface of nanoparticle

Question 3

How are Nanoparticles formed

2 Approaches

Answer 3

1. Top Down
   
   • Start with a big particle
   • Particle is broken down into smaller particles by mechanical forces until reach nanoscale
2. Bottom Up
   
   • Start from atomic / molecular level
   • Atoms come together + slowly grow to form nanomolecule

Question 4

What are the advantages of various nanomedicines

Answer 4

• Enhance drug stability, solubility, and bioavailability
• Improved CNS penetration
• Enhanced targetted drug delivery
  
  • due to surface modification with targeting ligands (also enhance BBB crossing)
• Reduced toxicity
  - drug is encapsulated (protected)
  - surface ligands = specificty = drug only goes to target tissue
• High loading capacity
• Controlled drug release

Question 5

What are the disadvantages of various nanomedicines

Answer 5

• Potential accumulation as not all nanoparticle may be removed from body
• Patient-specific repsonses
• Complex formulation process
• High drug loading isn’t guaranteed

Question 6

Example of nano fomulations

Answer 6

1. Drug encapsulated in LIPOSOMES
   - lipid based formulations = improved drug solubility + improved movement across BBB
2. Polymeric nanoparticles
   - encapsulate hydrophobic / lipophilic drug in core
   - improve solubility + stability
3. Solid lipid NANOPARTICLeS
4. Antibody Conjugate
5. Polymer-protein Conjugate

Question 7

How are lipid-based nanoparticles formed

inc. Liposomes and Lipid nanoemulsions

Answer 7

Liposome:
- Have a phospholipid bilayer (with cholesterol attached)
- have hydrophillic core (hydrophillic heads + hyrophobic tails)

Lipid Nanoemulsion:
- Start with lipid nanoemulsion
- NOT phospolipid bilayer
- can from: Solid lipid nanoparticle OR Nanostructure lipid carrier
- HAve surfactanst on surface
-

Question 8

Polymeric nanoparticles

Subcategories, how they’re formed

Answer 8

3 Subcategories:
1. Micelle systems (circular structure)
- normal micelles = hydrophillic head facing the solution + hydrophobic tail inwards (protected)
- put hydrophobic drug in core = drug encapsulation
- formed in aqueous / water solution
- reverse micelles = hydrophobic tail facing ourwards + hydrophilic head inwards
- put hydrophillic drug in core
- formed in oil solutions
- wont form micelle if put in water

2. Dendrimers
   
   • drug is conjugated with a linker OR encapsulated inside
3. Solid nanoparticles

Question 9

Protein-based (Conjugate) Nanomedicines

Answer 9

• Conjugate protein to outside surface of nanoparticle