Site Specific Delivery

Question 1

Why is this important?

Answer 1

• drugs never reach there target due to short half life
• drugs have undesirable distributions around body
• drugs with low therapeutic indexes have poor solubility, stability and absorption

Question 2

Ideal properties

Answer 2

• reach the target site
• achieve therapeutic response
• prevent degedation before reaching target site
• will eventually biodegrade to avoid toxicity
• target recognition
• simple, cost effective, reproductable

Question 3

1. Extravasation

Answer 3

There are three biological process that are important

• remove from blood circulation
• depends on permeability or drug OR permeability of the transport system in use
• generally thing with LOW Molecular Weight end up in blood

-Differences between macromolecules and colloids

Question 4

2. Endocytosis

Answer 4

There are three biological process that are important

• Phago = solid
• Pino - fluid
• absorptive need a receptor

Question 5

3. Lymph

Answer 5

There are three biological process that are important

-generally HIGH molecular weight

Question 6

What are dendrimers?

why is DEP important?

Answer 6

synthetic polymers with branched structures used for drug delivery.

DEP (docetaxeel)

• used for breast cancer
• great because
  1. increase target ability
  2. increase efficacy of drug on cancer
  3. water soluble so there are no toxic parts
  3. Extend the half life

Question 7

Why are colloids used in this context?

Answer 7

• protection
• for drugs with poor solubility
• drug targeting
• alter PK profiles

Question 8

What is the size for colloid?

Answer 8

0.02 micron - 100 micron

Question 9

Explain the production of liposomes

Answer 9

Thin film hydration

1. evaporate solvent from lipid
2. Agitation forms Multimellar vesciles
3. Sonication forms Large Unilamellar vesclies
4. Further extrusion forms Small Unilamellar vescles

Question 10

Describe the pathways of liposomes

eg in the blood and interactions with cells

Answer 10

Blood:

• high density = destroyed
• oposins (antibodies) = uptake by mononuclear phagocyte system

Interactions with cells

1. Fusion with membrane
2. Adsorption to cell wall
3. endocytosis into cells

Question 11

What is shealth technology?

Answer 11

Graft hydrophobic polymers to the lipid bilayer
-this prevents the uptake by mononuclear phagocyte system (MPS)
thus drug stays in body for longer
-generally use PEG
-eg DOXIL from 12mins to 15 hrs

Question 12

How is targeting in Cancer treatment achieved?

Answer 12

1. EPR - Enhanced permeability and retention (meaning lack of lymphatic tissue and fenestrated cells increase blood flow and accumulation certain sized molecules
2. phagocytosis of liposomes
3. prolong circulation time using DOXIL (liposomes)

Question 13

How are immunoliposomes made?

Answer 13

1. Pepsin removes the Fc unit on the antibody
2. DTT cause reduction
3. bind the product to the liposome

Question 14

What are the pathways involved with immunoliposomes?

Answer 14

1. Uptake in liver- broken down then drug is released
2. released at the target
3. external trigger causes the drug to release
4. fusion with targe causing drug release

Question 15

Advantages of using liposomes as drug carriers

Answer 15

1.biodegradable
2.verstile
3.biologically inert
4.used for both phili/phobic
5.both passive/active targeting
6.prolong half life
7. protects drug
8reduces toxicity

(need at least 4)

Question 16

Disadvantages of using liposomes as drug carriers?

Answer 16

1. Stability - because liposomes arnt real solid the drug may leak out
2. rapidly cleared by MPS
   - low drug loading
   - poor control of drug release

Question 17

Different between macromolecules and colloids

Answer 17

Macro:
-soluble particles
-non-specific pinocytosis 
-pass through gaps in capillaries 
Colloids:
-insoluble particles
-escapes via feneserated/sinusoidal

both via receptor mediated transport