Advanced drug delivery 1

Question 1

What is the aim of drug delivery and targeting?

Answer 1

To deliver a certain drug to its precise site of action, avoiding all other tissues in the body, at the right concentration for the right time

Question 2

Drug release and drug plasma levels - Conventional dosage forms

Answer 2

Depend essentially on physicochemical properties of the API

Question 3

Drug release and drug plasma levels -
Non-conventional dosage forms

Answer 3

Determined by the technological characteristics of the formulation - e.g. MR, if drug release from formulation slow then drug delivery is also slow

Question 4

Drug release can be modified in terms of:

Answer 4

RATE: e.g. fast release, sustained release - depending on therapeutic application
TIME: e.g. how long after administration does drug release begin.
SPACE: drug release happens in specific areas - targeted

Question 5

Paul Ehrlich: Magic bullet approach

Answer 5

Concept of finding a selective target
Refers to an API that is POTENT and SELECTIVE i.e. kills the target in the human host without harming the host itself

Question 6

1st order targeting

Answer 6

Targeting an organ or tissue e.g. liver targeting

Question 7

2nd order targeting

Answer 7

targeting a certain type of cells e.g. tumour cells

Question 8

3rd order targeting

Answer 8

targeting an intracellular component e.g. lysosomes

Question 9

A pharmaceutical company has developed a novel technology that allows drug release only in the endosomes of kidney cells. Which type of targeting is this?

Answer 9

3rd order because it is targeting an intracellular component

Question 10

What are the three different approaches in drug targeting

Answer 10

Magic bullet: API is potent and selective
Prodrug: pharmacologically inactive derivative of the drug which is activated at site of action
Macromolecular carrier: carrier transports drug to site of action

Question 11

Magic bullet - Monoclonal antibodies

Answer 11

Antibodies = proteins produced in response to exposure to antigen
- Monoclonal antibodies (Mabs)
- Polycloncal antibodies
Considered as magic bullets because of their inherent capacity for specificity

Question 12

Monoclonal antibodies

Answer 12

Responsible for a single antigen

Question 13

Polyclonal

Answer 13

Responsible for more than one antigen

Question 14

Describe the structure of antibody

Answer 14

Two heavy chains (H)
Two light chains (L)
The chains are connected by disulphide bridges
Dotted areas at the tips are the antigen binding site (ABS)
Arms are the Fragment antigen binding (FAB) which contain the ABS

Question 15

3 examples of Mabs on the market

Answer 15

• OKT3
  First mab to reach market
  Anti-CD3 antibody
  Prevents rejection of kidney transplant
• Abciximab
  Prevents cardiac ischemic complications
• Trastuzumab (Herceptin)
  Treatment of HER2+ breast carcinoma

Question 16

Discuss the principle of using mabs as imaging agents

Answer 16

1. Identify antigen that is associated with a certain tumour.
2. Develop a monoclonal antibody that specifically targets this antigen.
   - Selective for this antigen.
3. An imaging agent can be attached to the monoclonal antibody.
4. Monoclonal antibody then binds to the antigen, and as it is linked to the imaging agent we are able to visualise/image these cells.

Question 17

3 commercial products using mabs as imaging agents

Answer 17

Oncoscint - colon and ovarian cancer
Prostascint - prostate cancer
Myosin - cardiac imaging

Question 18

What is a prodrug

Answer 18

Chemically and pharmacologically inactive derivative of the drug that undergoes activation at its target site

Question 19

Examples of how a prodrug may be activated

Answer 19

Chemically e.g. hydrolysis (like carboplatin)
Physically e.g. physical stimuli like heat
Enzymatically

Question 20

Why are prodrugs used

Answer 20

• Improved permeability through biological membranes (e.g. levodopa)
• Site-specific administration
• Increased duration of drug action
• Decreased toxicity and SE
• Improved formulation
• Improved organoleptic properties

Question 21

What is a macromolecular carrier

Answer 21

• Biologically inert macromolecule that is used to deliver the drug to the site of action
• Typically polymers
• Carrier may:
  Particulate carrier system
  Soluble macromolecular carrier
• Drug may be:
  Entrapped in the carrier (physical bonds)
  Covalently conjugated
• Body distribution of drug will depend on characteristics of carrier

Question 22

Macromolecular carriers - types of targeting

Answer 22

• Active
• Passive
• Physical

Question 23

Active targeting

Answer 23

There is an active targeting moiety that delivers the system

Question 24

Passive targeting

Answer 24

• Exploits the natural distribution of the carrier
• e.g. carrier may distribute to certain areas, possibly because of its size

Question 25

Physical targeting

Answer 25

Drug release is due to a physical stimulus