5. Drug delivery and gene therapy Flashcards Preview

Nanotechnology > 5. Drug delivery and gene therapy > Flashcards

Flashcards in 5. Drug delivery and gene therapy Deck (41)
Loading flashcards...
1

Why do we need drug delivery systems?

keep drug plasma levels between the minimal effective level and the maximal required level; the therapeutic window. for selectivity and for targeting.

2

There are 2 principles of controlled drug delivery systems. Which and give examples of each.

diffusion-controlled, example tablet semipermeable membrane in gastro-intestinal system, inhalation device (?) degradation-controlled, example: gels that release drug when GEL degrades.

3

Give examples of drug delivery systems.

inhalation devices, patches, tablets and injectables

4

How small is a nanoparticle? Give relative examples.

DNA (2.5 nm diam) - bacterium (2.5 microm, length) - large raindrop (2.5 mm) carbon nanotube ( 1 nm, diam) - hair (0.1 mm) - house (10 m)

5

What are quantum dots?

No idea

6

Give 5 examples of organic NPs and 4 examples of inorganic NPs.

polymeric NPs, micelle, liposome, nanogel, dendrimer. magnetic NP, mesoporous silica, gold NP, quantum dot

7

What is the "smartest" NP nature has made? Describe how it looks like and how it works.

virus (approx 100 nm) - nucleoprotein (with RNA) - capsid - lipid envelope - proteins on outer core (eg neuraminidase , hemagglutinin) -infection: endocytosis - uncoating - to nucleus - replication - transcription: outside the nucleus translation to viral proteins - maturation in Golgi - expression on cell membrane inside the nulceus: RNA is packaged with ribonucleoprotein core - move outside nucleus - budding - virus exocytosis (name correct?) with cell membrane with viral proteins on it.

8

Give 3 examples of nanoparticles designed for drug delivery.

1) amphiphilic copolymer with hydrophobic drug: polymeric micelle 2) polymer with pendant drug: self assembly to NP 3) lipids with drug : liposomes.

9

What is a polymeric micelle?

micelle formed from amphiphilic copolymers.

10

Give examples of drug conjugates with polymers.

drug itself is polymer (?) protein - polymer polymer-DNA complex (with hydrophilic block and cationic block) polmer - drug conjugate (with linker in between) polymeric micelle (with hydrophilic block and hydrophobic block)

11

Give an example of the use of a polymer drug conjugate in the treatment of a disease. What is the purpose of conjugation with a polymer?

PEGylation of interferon prolonged the half life in plasma and could be used for the treatment of hepatitis C. P.S: info from Wiki: Interferons (IFNs) are a group of signaling proteins made and released by host cells in response to the presence of pathogens, such as viruses, bacteria, parasites, or tumor cells. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses.

12

What is the advantage of molecular imaging in the treatment of tumours?

localisation and targeting the tumors. Localised therapy.

13

What is the chemical structure of PEG?

polyethyleneglycol H(OCH2CH2)nOH

14

Describe some general characteristics of the physiology of cancer.

1) high intake of nutrients (over-expression of receptors) 2) highly vascularised (leaky vessels) 3) acidic and reducing environment (tumor cells are acidic because of the high energy demand and consequently the anaerobe use of glucose) 4) gene mutations

15

What are the challenges in NP delivery?

1) barriers (removal by kidneys, liver, spleen; blood and cellular clearance) 2) opsonisation 3) endosomal trap 4) P-glycoprotein

16

Why is the "ideal" size of a NP for the purpose of drug delivery between 100 and 200 nm?

We need to ask, because there are differences between the different lecturers!!!

Natural clearance: kidneys (glomerular filtration): smaller than 5 nm liver (entrapment by Kupfer cells): smaller then 100 nm liver and spleen (reticulo-endothelial system): larger than 200 nm

17

What type of NPs are subject to opsonisation?

neutral or hydrophylic particles

18

Describe how an endosomal trap works.

endocytic vesicle - acidification inside the vesicle - destabilised membrane. Consequence: 1) membrane rupture and burst, or 2) pore formation, or 3) membrane fusion.

19

What is the name of the protein which pumps "unwanted" molecules out the cell?

P-glycoprotein

20

What is P-glycoprotein?

ATP-powered drug efflux pump. removes hydrophobic molecules.

21

There are 2 mechanisms by which we can target a NP to the place in the body where a drug should be delivered. Which mechanisms? How can you achieve targeting by each mechanism?

passive targeting: size of NP active targeting: ligand on NP

22

When making use of EPR, do you make use of active or passive drug targeting?

passive

23

Describe an example with a degradable polymer for the active targeting of cancer.

acid-degradable monomer plus functionalised monomer - polymer - particle formation with a protein antigen (?). In acidic environment (tumor) polymer degrades and antigen protein can destroy tumor cells. If I understood correctly.

24

How may you approach diseases due to a genetic mutation?

gene therapy; RNA interference

25

Describe how DNA damage in the cell may occur?

UV radiation thymine dimer formation endogenous sources of reactive oxygen species resulting in either tumor promotion and/or in depletion of cellular antioxidants - more mutations due to oxidative stress which cannot be counterbalanced by DNA repair.

26

What is a tumor suppressor gene? Give 2 examples.

gene which codes for proteins which prevent cell division or which lead to cell death (inhibition of mitosis) Rb gene (retinoblastoma) and p53

27

What is a proto-oncogene?

gene that codes for proteins which stimulate cell division. Examples: PD growth factor, some ras genes, something with myc and c-jun and c-fos

28

How may DNA damage lead to tumor formation?

in a tumor suppressor gene: mutation results in dysfuntioning of protein - the inhibition of cell division is blocked = cell growth in a proto-oncogene: mutation results in the gene always "on" = continuous cell division. Examples Ras family protein mutations present in certain cancer types.

29

Describe how siRNA can counteract the effects of over-expressed proteins?

siRNA - 5'phosphorylation - complex formation with RISC - siRNA unwinding - mRNA targeting - mRNA cleavage.

30

Design a siRNA drug. Which steps do you need to consider?

1) select correct siRNA (in silico, in vitro) 2) stabilise RNA (chemistry: backbone modification of the "overhang" and 2'-base sugar modification) 3) select delivery method (naked, PEG, liposome, cyclodextrine, dendrimer, peptide conjugated, antibody-siRNA chimera, aptamer -siRNA chimera, 3-way junction pRNA nanoparticle; iron oxide NP and DNA nanoparticle)