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SOM 3 > Intro to polymers > Flashcards

Intro to polymers Flashcards

1
Q

when are polymers used?

A

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

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2
Q

what are some examples of therapeutic polymers?

A

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

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

artificial tears

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3
Q

what are the types of morphology of polymers?

A

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

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4
Q

what are the types of copolymers

A
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5
Q

what are the types of non-linear/branched polymers

A

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

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6
Q

why is number of generations important for dendrimers?

A

THE LOWER the number of generations the LESS ISSUES with stability

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7
Q

what can NMR tell us about polymers?

A

an estimated MW
number of monomers estimation

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8
Q

why are nanomedicines coated with PEG ?

A

to mask hydrophobic drugs

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9
Q

how can polymers MW be determined?

A

size exclusion/ gel permeation chromotagraphy
LOOK AT NOTES FOR MORE

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10
Q

how are polymers thermal properties assessed?

A

DSC - differential scanning calorimetry

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11
Q

what are the design requirements for polymer-drug conjugates?

A
  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
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12
Q

what does it mean by polymers being electrostatic?

A

they can be ionised…
cationic/neutral/anionic polymers

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13
Q

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

A

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

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14
Q

polymer carriers must be…

A

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

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15
Q

which examples of polymer carriers aren’t biodegradable

A

HPMA or PEG

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16
Q

what are modifiable junctions?

A

branched
star-shaped
dendrimers

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17
Q

what is the EPR effect?

A

Enhanced permeation retention effect

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18
Q

what does the EPR effect mean for nanoparticles?

A

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

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19
Q

how do nanoparticles get removed from the site if action?

A

via the lymphatic system, which occurs slowly.

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20
Q

why is the MW important for the EPR effect?

A

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

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21
Q

whats the ideal nanoparticle size?

A

<60-100nm

bigger than kidney pore size (>5nm)

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22
Q

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

A
  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
23
Q

whats MPS?

A

m=mononuclear
p=phagocyte
s=system

24
Q

whats RES?

A

R=reticulo
e=endothelial
s=system

25
Q

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

A

MPS & RES

26
Q

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

A

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

27
Q

how do polymer micelles form?

A

amphiphilic polymer chains

28
Q

what do convention micelles do?

A

water soluble
deliver hydrophobic drugs
deliver polytonic therapeutic macromolecules

29
Q

what do reverse micelles do?

A

oil-soluble
deliver water-soluble macromolecules

30
Q

what are polymeric micelles (multi molecular) ?

A
  1. hydrophobic core (drug encapsulation)
    - ionisable/neutral
    - semi-crystalline/amorphous
  2. hydrophilic shell -stealth like properties
    - dense
    - generally made of PEG
31
Q

what should a core-forming block be?

could be?

A

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

32
Q

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

A
33
Q

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

A
34
Q

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

A
35
Q

what are the advantages of polymeric micelles?

A
  • 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
36
Q

what are the disadvantages of polymeric micelles?

A
  • 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

37
Q

what are the forces in micelles?

A
  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

38
Q

how does the drug become encapsulated in micelles?

A

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

39
Q

how can polymeric micelles be prepared?

A
  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
40
Q

describe dialysis method

A
41
Q

describe emulsion method

A
42
Q

describe polyion-complex micelles method

A
43
Q

polymeric micelle characterisation equations

A
44
Q

polymeric micelle characterisation

A
  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
45
Q

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

A

through critical association concentration (CAC)

shows the stability after iv injection

46
Q

what does CAC assess?

A

hydrophobicity
length
core properties
drug loading

47
Q

how is the polymeric micelles kinetic ability be assessed?

A

unimer exchange
cohesion
dissociation
core viscosity

48
Q

what happens if conc< CAC?

A

low fluorescent emission

49
Q

what happens if conc> CAC?

A

high fluorescent emission

50
Q

how can polymeric micelle kinetics be measured?

A

FRET - flourescent probes/fluoroscence quenching

51
Q

how does FRET work?

A
52
Q

whats the other stability issues associated with micelles

A

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

53
Q

drugs are released from micelles through…

at the site of action…

A

thru…
diffusion
degradation
dissociation

at the site of action…
endocytosis
extracellular/intracellular release

SOM 3 (26 decks)

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