Intro to polymers

Question 1

when are polymers used?

Answer 1

suspending agents - to allow swelling in water
- polysaccharides
- cellulose
semi-solids (gels)
mucoadhesion
modified release (matrix/coating)
tablet manufactoring (binders/disintegrants)/coating
plasticises/solvents
capsule shell
emulsifiers
packaging

Question 2

what are some examples of therapeutic polymers?

Answer 2

Sodium polystyrene sultanate (Resonium A) - treatment of hyperkalaemia; oral/rectal admin

Poly(ethylene glycol) (- MOVICOL) - treatment of constipation

artificial tears

Question 3

what are the types of morphology of polymers?

Answer 3

homopolymer - single monomer
copolymer - chain of two or more monomers
non-linear/branched polymers
dendrimers -circular shaped

Question 4

what are the types of copolymers

Answer 4

Question 5

what are the types of non-linear/branched polymers

Answer 5

star-shaped polymers
graft (on both sides) copolymers
comb (on one side) polymers

Question 6

why is number of generations important for dendrimers?

Answer 6

THE LOWER the number of generations the LESS ISSUES with stability

Question 7

what can NMR tell us about polymers?

Answer 7

an estimated MW
number of monomers estimation

Question 8

why are nanomedicines coated with PEG ?

Answer 8

to mask hydrophobic drugs

Question 9

how can polymers MW be determined?

Answer 9

size exclusion/ gel permeation chromotagraphy
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Question 10

how are polymers thermal properties assessed?

Answer 10

DSC - differential scanning calorimetry

Question 11

what are the design requirements for polymer-drug conjugates?

Answer 11

1. water soluble backbone = increases aqueous solubility
2. drug conjugation - for target site delivery
3. targeting moiety - enhance binding/uptake
4. high MW - increases EPR effect = lower elimination via filtration

Question 12

what does it mean by polymers being electrostatic?

Answer 12

they can be ionised…
cationic/neutral/anionic polymers

Question 13

what are some examples of cationic/neutral/anionic polymers?

Answer 13

cationic = poly(lysine)
neutral = PEG, HPMA, dextran
anionic = Poly(aspartic acid), poly(glutamic acid)

Question 14

polymer carriers must be…

Answer 14

biodegradable
biocompatible
large enough to avoid kidney excretion (EPR effect)
sufficient number of modifiable junctions

Question 15

which examples of polymer carriers aren’t biodegradable

Answer 15

HPMA or PEG

Question 16

what are modifiable junctions?

Answer 16

branched
star-shaped
dendrimers

Question 17

what is the EPR effect?

Answer 17

Enhanced permeation retention effect

Question 18

what does the EPR effect mean for nanoparticles?

Answer 18

nanoparticles don’t target a specific site.
we must increase the retention time of the drug in systemic circulation to allow the drug conjugates to accumulate at the site of action. this occurs via the EPR effect

Question 19

how do nanoparticles get removed from the site if action?

Answer 19

via the lymphatic system, which occurs slowly.

Question 20

why is the MW important for the EPR effect?

Answer 20

so that the particle can be bigger than the kidney pore size (>5nm), increasing systemic circulation retention

Question 21

whats the ideal nanoparticle size?

Answer 21

<60-100nm

bigger than kidney pore size (>5nm)

Question 22

how do polymer-drug conjugates get eliminated by the blood?

Answer 22

1. glomerular filtration
2. removal by the body defences (MPS/RES)
   
   • occurs mainly for large, hydrophobic or charged nanoparticle
3. polymer degradation via enzymes
4. accumulation in healthy tissue
   
   • thru capillary fenestrations (2-6nm) and removed thru the lymphatic system
5. accumulation in tumour vicinity
   
   • thru EPR effect and removed thru the lymphatic system

Question 23

whats MPS?

Answer 23

m=mononuclear
p=phagocyte
s=system

Question 24

whats RES?

Answer 24

R=reticulo
e=endothelial
s=system

Question 25

what are the ways to remove drug delivery systems in the blood?

Answer 25

MPS & RES

Question 26

what are factors that effect accumulation/elimination of polymer-drug conjugates?

Answer 26

polymer flexibility and morphology - rigid, tubular polymer chains increase accumulation - elongated flexible polymers increase renal filtration and decrease circulation times - spherical rigid polymers decrease renal filtration and increase circulation times

Question 27

how do polymer micelles form?

Answer 27

amphiphilic polymer chains

Question 28

what do convention micelles do?

Answer 28

water soluble deliver hydrophobic drugs deliver polytonic therapeutic macromolecules

Question 29

what do reverse micelles do?

Answer 29

oil-soluble deliver water-soluble macromolecules

Question 30

what are polymeric micelles (multi molecular) ?

Answer 30

1. hydrophobic core (drug encapsulation) - ionisable/neutral - semi-crystalline/amorphous 2. hydrophilic shell -stealth like properties - dense - generally made of PEG

Question 31

what should a core-forming block be? could be?

Answer 31

biodegradable hydrophobic enough to interact with the drug could be... attached at the end of the chain - block copolymer distributed along the chain - graft copolymer

Question 32

what are biodegradable poly(esters) core forming polymers and draw the structures

Answer 32

Question 33

what are less common hydrophobic moieties core forming polymers and draw the structures

Answer 33

Question 34

what are common hydrophilic moieties shell forming polymers and draw the structures

Answer 34

Question 35

what are the advantages of polymeric micelles?

Answer 35

* Solubilisation of hydrophobic drugs * Protection of loaded drug * Solubilisation via complexes * Small size - Sterilisation by filtration - EPR effect - Long circulation times * Colloidal solution - Easy to detect precipitates

Question 36

what are the disadvantages of polymeric micelles?

Answer 36

* Preparation requires organic solvents * Lack of stability MAIN ISSUE - Thermodynamic -Dissociation at C < CMC - Problem for administration -Dilution in blood +++ - Kinetic - Rate of dissociation -Crystalline structure Therefore hard to produce

Question 37

what are the forces in micelles?

Answer 37

1. hydrophobic forces - between the core and insoluble drug 2. electrostatic forces (polygon complex micelles) 3. metal co-ordination (platinum drug micelles) 2&3 - increase hydrophobic forces = formation of micelles

Question 38

how does the drug become encapsulated in micelles?

Answer 38

chemical conjugation- covalent binding of the drug to the core-forming polymer (releases at a controlled degradation rate) physically 1. direct encapsulation 2. micelle preparation -drug added in organic phase

Question 39

how can polymeric micelles be prepared?

Answer 39

1. dialysis method 2. emulsion method 3. film formation - polymer dissolved with a volatile organic solvent 4. sonication - encapsulated using ultrasonic probe 5. co-ordination of micelles

Question 40

describe dialysis method

Answer 40

Question 41

describe emulsion method

Answer 41

Question 42

describe polyion-complex micelles method

Answer 42

Question 43

polymeric micelle characterisation equations

Answer 43

Question 44

polymeric micelle characterisation

Answer 44

1. Aggregation number - determine MW 2. all particle size - light scattering/microscopy 3. surface charge - Ζ charge (+'ve charge - DNA conjugation, -'ve charge - target liposomes) 4. micellisation - unimers into micelles. linked to stability

Question 45

how can polymeric micelles stability be assessed? why is it important?

Answer 45

through critical association concentration (CAC) shows the stability after iv injection

Question 46

what does CAC assess?

Answer 46

hydrophobicity length core properties drug loading

Question 47

how is the polymeric micelles kinetic ability be assessed?

Answer 47

unimer exchange cohesion dissociation core viscosity

Question 48

what happens if conc< CAC?

Answer 48

low fluorescent emission

Question 49

what happens if conc> CAC?

Answer 49

high fluorescent emission

Question 50

how can polymeric micelle kinetics be measured?

Answer 50

FRET - flourescent probes/fluoroscence quenching

Question 51

how does FRET work?

Answer 51

Question 52

whats the other stability issues associated with micelles

Answer 52

destabilisation of serum proteins in the presence of salts influenced by HLB

Question 53

drugs are released from micelles through... at the site of action...

Answer 53

thru... diffusion degradation dissociation at the site of action... endocytosis extracellular/intracellular release