Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Drug Delivery > Targeted Delivery > Flashcards

Targeted Delivery Flashcards

1
Q

What is the rationale for the development of targeted drug delivery systems (TDDSs)? [4]

A
  1. Magic bullet to target the drug to specific target cells or target tissues.
  2. Minimises loss of drug during transit to target - retained within TDDS. Protects the drug from premature clearance.
  3. Retains drug at target site for prolonged period of time.
  4. Can facilitate intracellular delivery if required.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is active targeting?

A

Target the drug solely to diseased tissue by knowing the nature of a receptor that is only present on cells which we wish the drug to bind to.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What strategies can be used to achieve active targeting?

A
  1. Avidin-biotin
  2. Antibody targeting and the use of Ab fragments.
  3. Affibodies
  4. Aptamers
  5. Ligand receptor interactions
  6. Magnetic localisation and delivery.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the EPR effect?

A

Tumour vasculature is leaky. Macromolecules and nanoparticles can permeate tumour tissue because the blood vessels that feed into and run through the tumours are leaky. Tight junctions are not so tight etc. Also poor drainage and removal by the lymph system.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How can we improve the accumulation of TDDS via the EPR effect?

A

Induce hypertension -> increase leakage into tumour tissues.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is an affibody?

A

Small proteins engineered to bind to a large number of target proteins or peptides with high affinity, imitating antibodies. Easily generated. HER-2 targeting via affibodies has occurred.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is an aptamer? [5]

A
  1. Oligonucleotide or peptide molecules that bind to specific target molecules.
  2. Chemical equivalent of antibodies.
  3. Created using SELEX.
  4. Can be added to liposomes etc. for targeted delivery.
  5. Mucagen: aptamer/RNA treatment.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is SELEX? [6]

A

Process for creating aptamers.

  1. Synthetic ssDNA aptamer library is mixed with a culture of a patient’s lymphoma cells.
  2. Unbound ssDNA aptamers are washed away and PCR amplification of those that bound takes place.
  3. This aptamer pool is then mixed with control cells.
  4. Any aptamer which binds to the control cells are discarded. Unbound aptamers are selected and amplified via PCR.
  5. We know have an aptamer pool of ssDNA which binds t lymphoma cells but not to normal healthy cells.
  6. These can then be added onto liposomes etc. for targeted delivery.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How can antibody-antigen targeting by utilised in targeted delivery? [3]

A
  1. Cell-surface antigens can become upregulated in certain cell types during certain disease states. Antibodies against these antigens can be used to target drug delivery just to the disease causing cells.
  2. For example PSA, HER-2, plasmin, CD44 (hyaluronic acid).
  3. ADEPT etc.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How can photodynamic therapy by used to treat HER-2 positive cancers?

A

Photosensitisers can accumulate in tumour tissue but also remain in circulation = non-specificity. Combining PSs with Ab can allow targeting of cancer cells or pathogens alone.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What antigens are often upregulated in certain disease states and can be targeted by antibody fragments?

A 
HER-2
PSA
Plasmin
CD44 (hyaluronic acid)
Lutenizing hormone releasing hormone receptor (LHRHr)
Folate receptor (FR)
Integrins.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How can avidin-biotin binding be used to target drug delivery?

A

i. Has successfully been used to clinically diagnose and treat tumours.
ii. Can be used to develop conjugated targeted drug delivery systems.
1. Biotinylated mAb for a specific cell surface receptor upregulated in cancer is developed and admin.
2. Biotinylated mAb binds to the tumour cell antigen.
3. Avidin binds to specific section of the biotinylated mAb,
4. Chemotherapeutic drug targeted to section of avidin is introduced to patients system.
5. Drug becomes bound to avidin/biotinylated mAb system which is attached to tumour cell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Why can targeting of integrins be used to treat cancers?

A

Integrins are cell surface glycoproteins that mediate cell-cell and cell-matrix interactions and integrin expression is upregulated in many cancers. Ligands that bind to integrins can be used to specifically target drugs to tumours.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is RGD?

A

Arg-Gly-Asp tripeptide. Found in collagem, fibronectin and laminin is recognised by integrins.
RGD and its derivative are widely used in targeting.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Why is RGD and its derivatives widely used in cancer targeting?

A

Arg-Gly-Asp (RGD) tripeptide is found in collagen, fibronectin and laminins. Recognised by integrins.

Therefore we can incorporate this structure into drugs and they will be bound by integrins.

Integrins are commonly overexpressed on tumour cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is Arg-Gly-Asp?

A

Arg-Gly-Asp (RGD) tripeptide is found in collagen, fibronectin and laminins. Recognised by integrins.

Therefore we can incorporate this structure into drugs and they will be bound by integrins.

Integrins are commonly overexpressed on tumour cells.

17
Q

Examples of strategies to exploit the EPR effect:

A

Use of STEALTH liposomes.

Hypertension induction: increased accumulation.

18
Q

How can magnetic localisation be used for drug targeting?

A

A magnetic field interaction can cause the release of drug from a specialised polymer drug matrix.

19
Q

What is the main problem in the use of liposomes as drug delivery vehicles in vivo?

A

They are rapidly cleared by the RES system. To combat this, PEG can be added to the surface of the liposomes.

20
Q

How are micelles created?

A

They consist of certain amphiphillic co-polymers consisting of both hydrophobic and hydrophilic monomer units.

21
Q

What are dendrimers?

A

Polymer-based delivery vehicles, they have a core that branches out in regular intervals to form a small, spherical and very dense nanocarrier.

22
Q

What are the ideal properties of a TDDS?

A
  1. Targets the drug to specific cells or target tissues.
  2. Keeps the drug away from non-target cells, organs or tissues.
  3. Minimises loss of drug during the transit to target
  4. Protects the drug from premature clearance.
  5. Retains drug at target site for the required period of time.
  6. Facilitates intracellular delivery to the site (if required)
  7. Is biocompatible, biodegradable, and non-antigenic.
23
Q

What is the difference between soluble and particulate carriers?

A

Soluble:
Drug is covalently attached and then released though chemical reaction.
Readily extravasate, depending on the MW.
Limited loading capacity (although pendant systems increase this).
Limited protection of drug.

Particulate:
Drug can be physically-associated or covalently attached.
Release can occur through chemical reaction, diffusion, pH change, temperature, magnetism.
High drug loading
Good protection
Can not cross intact epithelia
Need to avoid phagocytosis unless targeting macrophages.

24
Q

Why do long-circulating macromolecules, such as polymer conjugates, micelles, liposomes and nanoparticles, accumulate in solid tumours?

A

The EPR effect.

25
Q

What type of carrier can allow drug release via chemical reaction, diffusion, pH change, temperature, magnetism?

A

Particulate.

26
Q

What are the disadvantages of using particulate carriers for drug delivery?

A

Can not cross intact epithelia

Need to avoid phagocytosis unless targeting macrophages.

27
Q

What are the disadvantages of using soluble carriers for drug delivery?

A

Limited loading capacity (although pendant systems increase this).
Limited protection of drug.

28
Q

What are the benefits of using particulate carriers for drug delivery?

A

Drug can be physically-associated or covalently attached.
Release can occur through chemical reaction, diffusion, pH change, temperature, magnetism.
High drug loading
Good protection

29
Q

What are STEALTH liposomes?

A

Make use of the EPR effect.
>90% of drug remains in the liposome within circulation.
Clinically effective, shrinking or preventing progression of tumors.

30
Q

What is PDEPT?

A

Polymer-directed enzyme prodrug therapy.
A novel two-step antitumour approach using a combination of a polymeric prodrug and polymer-enzyme conjugate to generate cytotoxic drug selectively at the tumour site.

PDEPT uses polymer-drug conjugates, drugs contained within a polymer ‘shell’ such as pHPMA and designed to be released only by a specific enzyme.

31
Q

What is CDEPT?

A

CDEPT is the use of Clostridia to convert prodrugs into active drug agents. CDEPT exploits the hypoxic environment of solid tumors to target drugs to tumors using anaerobic bacteria resident in the tumour to convert the pro-drug to the active form.

So far, two enzymes have been applied in CDEPT: cytosine deaminase and nitroreductase.

32
Q

What passive targeting approaches are there?

A

Prodrug approach
Hypoxia-sensitive drugs
Acid-sensitive linkers

33
Q

How is the prodrug approach used in passive targeting?

A

Bacteria: Colal - ranitidine delivery. Sulphasalazine for ulcerative colitis.

Enzymes:
B-glucuronidase is highly expressed in the inflammatory cells in the necrotic region of tumours.

Proteases are often overexpressed in tumours so conjugation of amino acids can be used in produrg approaches. Leu-Dox.

PSA: serine protease highly expressed in prostate cancer cells.

Cathespins.

34
Q

A polymer shell, such as pHPMA, is commonly found in use in what?

A

PDEPT.
Polymer-directed enzyme prodrug therapy.
A novel two-step antitumour approach using a combination of a polymeric prodrug and polymer-enzyme conjugate to generate cytotoxic drug selectively at the tumour site.

PDEPT uses polymer-drug conjugates, drugs contained within a polymer ‘shell’ such as pHPMA and designed to be released only by a specific enzyme.

35
Q

What enzymes can be targeted in the prodrug passive targeting approach?

A

B-glucuronidase
Proteases: Leu-Dox
PSA: serine protease in prostate cancer cells.
Cathespins

36
Q

Why can hypoxia-sensitive drugs be used in passive targeting?

A

Tumours have regions of hypoxia and drugs sensitive to this environment can thus be used.

Relies on reductive enzymes, CYPs, to generate radical.

In oxic cells, the radical is back-oxidised to the drug by molecular oxygen. This cannot happen in hpyoxic cells so the radicals go on to damage DNA and kill the cell.

37
Q

Why can acid-sensitive linkers be used in passive targeting?

A

The tumour environment can be 0.5 - 1.0 pH units lower than normal tissues, therefore acid-sensitive linkers can be designed to release drug in the acidic conditions in tumours.

Example being Aldoxorubicin.

38
Q

What is the SMVT?

A

Sodium-dependent multivitamin transporter.

Biotinylated carriers can be used to target SMVT.

Drug Delivery (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions