Topic 2L Future Directions Of Drug Delivery And Targeting

Question 0

Describe the use of ADEPT as an approach for achieving cell specific drug delivery. illustrations (5)

Answer 0

Antibody-directed enzyme prodrug therapy
Target drugs to specific cells through their specific surface ligands.
Used to target tumour cells by employing an enzyme (not normally present) conjugated to an anti tumour antibody which localises the tumour by an antibody-antigen interaction.
A prodrug that is activated by the enzyme is then administered
The prodrug is only activated at the tumour site where it is converted into the cytotoxic parent compound. This localisation reduces systemic toxicity.
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Question 1

Describe the Use of prodrugs as site-specific delivery systems in the treatment of tumour cells (6)

Answer 1

1. Release the active drug only at its site of action
2. Site specific delivery to tumour cells exploit the unique microenvironment of the tumour (enhanced enzyme activity)
3. Blood supply to large solid tumours is disorganised- the internal regions are non-vasculated and deprived of oxygen. This enhances reductive activity

Question 2

Describe the use of biosensors in addressing the challenge of chronophamacology (7)

Answer 2

• ** A biosensor is a device integrated within or associated with a physical transducer.
  1. Catalytic biosensors: use enzymes, microorganisms or whole cells to catalyse a reaction with a target analyte.
  2. Affinity biosensors: use enzymes, receptors or nucleic acids to bind with an analyte.

Question 3

Limitations of implanted biosensors (4)

Answer 3

• *1. Biofouling
  2. Conditioning of biosensors with serum proteins (reduces the sensitivity and longativity)
  3. Encapsulation due to inflammatory response

Question 4

Describe the use of glucose sensing hydro gels in bio responsive drug delivery (5)

Answer 4

A highly specific interaction between glucose and concanavalin A is used to form a physical cross link between glucose containing polymer chains.

Increased glucose levels = gel becomes a sol (insulin releases quicker)
Decreased glucose levels = the competition of free glucose against polymer glucose decreases and the gel is formed again

Diffusion of insulin is much slower in the gel than sol therefore, insulin release is controlled dependent on glucose concentration

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Question 5

Describe. The use of genetically engineered cell implants in drug delivery

Answer 5

• **1. Use endogenous control systems to regulate delivery of a therapeutic protein
  2. Introduce a functional gene using viral or nonviral vectors into impaired cells that can not produce necessary proteins
  3. Enables the body to generate the required enzyme
  4. Second type gene therapy which uses surrogate cells
  5. Genetic modification of heterologous cells allows the surrogate cells to provide the body with necessary proteins