Intro to polymers Flashcards
when are polymers used?
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
what are some examples of therapeutic polymers?
Sodium polystyrene sultanate (Resonium A) - treatment of hyperkalaemia; oral/rectal admin
Poly(ethylene glycol) (- MOVICOL) - treatment of constipation
artificial tears
what are the types of morphology of polymers?
homopolymer - single monomer
copolymer - chain of two or more monomers
non-linear/branched polymers
dendrimers -circular shaped
what are the types of copolymers
what are the types of non-linear/branched polymers
star-shaped polymers
graft (on both sides) copolymers
comb (on one side) polymers
why is number of generations important for dendrimers?
THE LOWER the number of generations the LESS ISSUES with stability
what can NMR tell us about polymers?
an estimated MW
number of monomers estimation
why are nanomedicines coated with PEG ?
to mask hydrophobic drugs
how can polymers MW be determined?
size exclusion/ gel permeation chromotagraphy
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how are polymers thermal properties assessed?
DSC - differential scanning calorimetry
what are the design requirements for polymer-drug conjugates?
- water soluble backbone = increases aqueous solubility
- drug conjugation - for target site delivery
- targeting moiety - enhance binding/uptake
- high MW - increases EPR effect = lower elimination via filtration
what does it mean by polymers being electrostatic?
they can be ionised…
cationic/neutral/anionic polymers
what are some examples of cationic/neutral/anionic polymers?
cationic = poly(lysine)
neutral = PEG, HPMA, dextran
anionic = Poly(aspartic acid), poly(glutamic acid)
polymer carriers must be…
biodegradable
biocompatible
large enough to avoid kidney excretion (EPR effect)
sufficient number of modifiable junctions
which examples of polymer carriers aren’t biodegradable
HPMA or PEG
what are modifiable junctions?
branched
star-shaped
dendrimers
what is the EPR effect?
Enhanced permeation retention effect
what does the EPR effect mean for nanoparticles?
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
how do nanoparticles get removed from the site if action?
via the lymphatic system, which occurs slowly.
why is the MW important for the EPR effect?
so that the particle can be bigger than the kidney pore size (>5nm), increasing systemic circulation retention
whats the ideal nanoparticle size?
<60-100nm
bigger than kidney pore size (>5nm)
how do polymer-drug conjugates get eliminated by the blood?
- glomerular filtration
- removal by the body defences (MPS/RES)
- occurs mainly for large, hydrophobic or charged nanoparticle
- polymer degradation via enzymes
- accumulation in healthy tissue
- thru capillary fenestrations (2-6nm) and removed thru the lymphatic system
- accumulation in tumour vicinity
- thru EPR effect and removed thru the lymphatic system
whats MPS?
m=mononuclear
p=phagocyte
s=system
whats RES?
R=reticulo
e=endothelial
s=system
what are the ways to remove drug delivery systems in the blood?
MPS & RES
what are factors that effect accumulation/elimination of polymer-drug conjugates?
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
how do polymer micelles form?
amphiphilic polymer chains
what do convention micelles do?
water soluble
deliver hydrophobic drugs
deliver polytonic therapeutic macromolecules
what do reverse micelles do?
oil-soluble
deliver water-soluble macromolecules
what are polymeric micelles (multi molecular) ?
- hydrophobic core (drug encapsulation)
- ionisable/neutral
- semi-crystalline/amorphous - hydrophilic shell -stealth like properties
- dense
- generally made of PEG
what should a core-forming block be?
could be?
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
what are biodegradable poly(esters) core forming polymers and draw the structures
what are less common hydrophobic moieties core forming polymers and draw the structures
what are common hydrophilic moieties shell forming polymers and draw the structures
what are the advantages of polymeric micelles?
- 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
what are the disadvantages of polymeric micelles?
- Preparation requires organic solvents * Lack of stability MAIN ISSUE
- Thermodynamic
-Dissociation at C < CMC- Problem for administration
-Dilution in blood +++
- Problem for administration
- Kinetic
- Rate of dissociation
-Crystalline structure
- Thermodynamic
Therefore hard to produce
what are the forces in micelles?
- hydrophobic forces - between the core and insoluble drug
- electrostatic forces (polygon complex micelles)
- metal co-ordination (platinum drug micelles)
2&3 - increase hydrophobic forces = formation of micelles
how does the drug become encapsulated in micelles?
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
how can polymeric micelles be prepared?
- dialysis method
- emulsion method
- film formation - polymer dissolved with a volatile organic solvent
- sonication - encapsulated using ultrasonic probe
- co-ordination of micelles
describe dialysis method
describe emulsion method
describe polyion-complex micelles method
polymeric micelle characterisation equations
polymeric micelle characterisation
- Aggregation number - determine MW
- all particle size - light scattering/microscopy
- surface charge - Ζ charge (+’ve charge - DNA conjugation, -‘ve charge - target liposomes)
- micellisation - unimers into micelles. linked to stability
how can polymeric micelles stability be assessed? why is it important?
through critical association concentration (CAC)
shows the stability after iv injection
what does CAC assess?
hydrophobicity
length
core properties
drug loading
how is the polymeric micelles kinetic ability be assessed?
unimer exchange
cohesion
dissociation
core viscosity
what happens if conc< CAC?
low fluorescent emission
what happens if conc> CAC?
high fluorescent emission
how can polymeric micelle kinetics be measured?
FRET - flourescent probes/fluoroscence quenching
how does FRET work?
whats the other stability issues associated with micelles
destabilisation of serum proteins in the presence of salts
influenced by HLB
drugs are released from micelles through…
at the site of action…
thru…
diffusion
degradation
dissociation
at the site of action…
endocytosis
extracellular/intracellular release
