Pharmaceutical Nanotechnology and Nanomedicines

Question 1

Nanotechnology

• Is there a definition by the FDA?

Answer 1

• No established definitions by the FDA
• These terms are commonly used in relation to the engineering of materials that have at least one dimension in the size range of approximately 1 nm to 100nm

Question 2

Nanotechnology

• What does the National Nanotechnology Initiative Program define nanotechnology as?

Answer 2

• The understanding and control of matter at dimensions between approximately 1 and 100nm where unique phenomena enable novel applications

Question 3

What are the Pharmaceutical Applications and Key Priniciples of Nanotechnology?

Answer 3

• Enhanced solubility and dissolution because of high surface area to volume ratio
• Enhanced drug delivery carrier system
  
  • Modify these carriers to increase drug distribution, targeting and transport due to lower particle size
• Improved stability of therapeutic agents

Question 4

• What is a Polymer Drug Conjugate?
• Functions?

Answer 4

• Combination of drug and a polymer < 100nm
• Functions
  
  • Improve solubility of whole system
  • Enhance plasma half-life, limit for renal clearance is 45kDa so the clearance for a conjugate is reduced due to increased molecular weight
  • Protecting from degradation
  • Reducing immunogenicity
  • Targetging to specific organs

Question 5

What are the 3 Components of Polymer Drug Conjugates?

Answer 5

• Polymer, linker and drug
• Polymer is natural or synthetic
  
  • PEG is commonly used because of low polydispersity, immunogenicity and toxicity
  • PEG is easy to conjugate and very useful for improving solubility
• Linker group (e.g. amide, carbamate)
  
  • Protects therapeutic action of drug
  • Can be designed to degrade with change in pH, enzyme or hydrolysis

Question 6

What common drugs are used in polymer drug conjugates?

Answer 6

• Anticancer drugs such as doxorubicin, paclitaxel and proteins e.g. L-asparginase

Question 7

Micelles

• What are they?
• Size?

Answer 7

• Liposomes formed due to self assembly of surfactant molecules in aqueous environment
  
  • Hydrophobic core and hydrophilic surface
• Size typically <100nm

Question 8

Self Nano-Emulsifying Drug Delivery Systems (SNEDDS)

• What are they composed of?
• What happens upon ingestion?
• What do they offer?

Answer 8

• Composed of optimised mixture of oil, surfactants and drug
• Upon ingestion, the mixtures forms an oil in water emulsion with GI contents, at nanoscale range
• Offer better dissolution, greater surface for absorption and bioavailability

Question 9

Solid Nanoparticles

• What are they and how are they prepared?
• Increase in surface area corresponds to what?
• What is a potential problem?

Answer 9

• Solid particles in nano size range, prepared by size reduction or precipitation
• Increase in surface area corresponds to an increase in solubility, leading to improved dissolution and bioavailability
• Aggregation of particles is potential problem, which is solved by using surfactants

Question 10

What are the Types of Solid Nanoparticles?

Answer 10

• Solid Polymeric Nanoparticles
• Solid Lipid Nanoparticles or Solidified o/w Emulsions
• Protein Nanoparticles
• Inorganic Nanoparticles

Question 11

Types of Solid Nanoparticles

How are Solid Polymeric Nanoparticles formed?

Answer 11

• Formed from polymers with the drug incorporated within polymer matrix
• Natural and synthetic polymers used including biodegradable

Question 12

Types of Solid Nanoparticles

How are Solid Lipid Nanoparticles or Solidified O/W Emulsions formed?

Answer 12

1. Melting of lipid and dissolving the drug in the melted lipid
2. Dispersing the lipid - drug mix in the hot aqueous phase
3. Homogenisation or ultra high sonication above melting point of lipid
4. Hot O/W - nanoemulsion
5. Solidification of lipid by cooling down to room temperature
6. Lipid Nanoparticles

Question 13

Types of Solid Nanoparticles

How are Inorganic Nanoparticles formed?

Answer 13

• Fabricated using metal oxides, metal sulphides, ceramics and calcium phosphate
• Primarily used in diagnostics

Question 14

Discuss Enhanced Permeability and Retention (EPR) Effect in Cancer

Answer 14

Refers to how drugs can easily enter the tumour by passing through the gaps in the blood vessels, but cannot leave easily due to the poor lymphatic drainage

Question 15

What are the Safety Concerns with Nanotechnology?

Answer 15

• Potential for increased exposure of people and other living organisms to nano-sized particles
• Because of greater surface to volume ratio and increased surface functionality, nanoparticles offer greater biological activity leading to health and environment concerns

Question 16

What are 7 Challenges for Nanomedicine?

Answer 16

1. Determination of the nanoparticles distribution following systemic administration
2. Development of imaging modalities for measuring biodistribution
3. Mass transport across compartmental barriers in the body
4. Need for mathematical models
5. Computer models for predicting risk benefit
6. Establishment of reference standards
7. Analytical toolkit for nanopharmaceuticals