Synthesis of Nanomedicines Flashcards
what are the 2 categories of nanomedicines that will be focused on
solid drug nanoparticles
nanocarriers
what are polymers made up of
a chain of multiple monomers
what are the 2 ways of making polymers
chain growth
step growth
describe the process of chain growth
adding monomers to the end of the polymer chain
describe the process of step growth
using a monomer with 2 functional ends growth can occur in both directions
what type of monomers are used in chain growth
molecules with alkenes form the carbon backbone
what monomers are used for step growth of polymers
bifunctional molecules like amino acids
what is the degree of polymerisation
chain length (number of monomers in chain)
what is a polymer therapeutic
polymers where an active drug makes up more than 50% of the polymer
give an example of a therapeutic polymer and describe how the drug is released in the body
aspirin or morphine polymer
polymer is hydrolysed to yield drug
what is a dendrimer and how can it bind to pathogens
highly branched polymer
has many binding sites for pathogen to bind
how do polymer drug conjugates work
drug is bound to polymer backbone by spacer (PEG)
what advantages are there of using polymer drug conjugates and give an example
may reduce toxicity via enhanced permeation and retention
doxorubicin is an example
how are polymer micelles formed
PEGylation of drug to make drug surfactants
what can be added to aid amine conjugation
N-succinimidyl carbonate
how do polymers act as surfactants when bound to a drug
if drug is hydrophobic the polymer acts as the hydrophilic section and forms micelles above the CMC
how does the length of a polymer chain effect the activity of the chain ends
in longer chains the concentration of chain ends is lower
heavy polymers coil so the chain ends can be harder to find
how can gold nanoparticles be used as nanocarriers
can be stabilised by surface adsorbed molecules (PEG)
these can undergo exchange with drugs
exchange can be tuned
give an example of how gold nanoparticles as nanocarriers can be tuned
ligands can chelate with radioactive materials as part of radiotherapy
describe multifunctional AuNPs as radiotherapy
thioterminated antibodies target breast tumours
177Lu isotope on thiolated PEG
stabilised by thio-PEGs
how gold nanoshells be made
NH2 functionality given to Si NPs
AuNPs added
treated with AuCl4 and H2O2 to grow gold surface
how can goldnanoshell be used as an anticancer drug
if they accumulate in tumours they can be selectively heated and killed with rear-IR laser
what can be achieved by ring opening polymerisation
from cyclic ester when acted by PEG form long chain carbonyls can be generated
PEG group can then be modified as part of a surfactant
how can nonfunctionalized polymer surfactant be used
can form micelles that can contain hydrophobic drugs - doxorubicin
what can be achieved by mixing functionalised and nonfunctionalized polymers
mixed micelle is formed - properties can be tuned depending on polymer ratio
how can dialysis be used to assemble micelles
put polymer in good solvent within membrane
place membrane in water
solvent will exchange
fresh water is added and final organic solvent is removed
what property must a dialysis membrane have to form micelles
pores must be smaller than the molecular weight cut off (MWCO)
how can dendrimers be used as unimolecular micelles
has cavities within structure
can encapsulate hydrophobic drugs
what size are the droplets in nanoemulsions
10-100nm
describe the properties of a macroemulsion
> 1 micrometre
opaque
unstable
describe the stability of nanoemulsions
unstable
what are the droplet sizes in microemulsions
10-50nm
describe micro emulsions
stable emulsion
clear
how can emulsions be stabilised
by surfactants
what are solid lipid nanoparticles
similar to emulsion but with solid fat rather than droplets
how can solid lipid nanoparticles be made
mix lipid with drug and a solvent
emulsify into water
evaporate off organic solvent
forms homogenised emulsion as solvent evaporation reduces droplet size
what are some advantages of solid lipid nanoparticles
improved drug stability
control over drug release
lipids are biodegradable
relatively easy to scale
what is the main issue with solid lipid nanoparticles
lipid can crystallise without encapsulating drug - poor loading
what are 2 lab techniques that can be used to make solid lipid nanoparticles
homogenisation
ultrasonication
what is homogenation
process of making nanoparticles by pushing macroemulsion through small gap at high pressure
how can polymer nanoprecipitates be formed
amphiphilic polymers in organic solvent are quickly added to water
poorer solvent displacement leads to worsening environment
small structures assemble
structures aggregate
aggregation stops when colloidal stability is reaches
what factors effect the size of nanoprecipitates made
organic solvent and its conc miscibility of the polymer viscosity temperature rate of addition to antisolvent (water)
what are liposomes made up of
unimers with 1 hydrophilic head and 2 hydrophobic tails
how does the liposome bilayer form
interdigitation of hydrophobic tails
how can both hydrophilic and hydrophobic molecules be encapsulated in liposomes
hydrophilic molecules can reside in the core
hydrophobic molecules can be stored in the bilayer
what are some advantages of using liposomes
made of easily modifiable lipids
biodegradible
low immunoresponce
low toxicity
what are the disadvantages of liposomes
hydrophobic layer is thin
can be hard to encapsulate hydrophilic molecules
what are SUVs
small unilamellar vesicles <100nm
what are LUVs
large unilamellar vesicles 100-1000nm
what is a GUV
giant unilamellar vesicle
1-50 micrometres
what is a MLV
multilamellar vesicle (1-50 micrometres) double bilayer
what is MVV
multivesicular vesicles
liposomes in liposomes
1-50 micrometres
how are liposomes produced
phospholipid dissolved in organic solvent dried rehydrated with water gentle stirring produces MLVs processing gives LUV/SUV
give the properties of neat doxorubicin
highly toxic
administered as Cl salt
has 3 different pKa values
self assembles in water via pi stacking
what are the advantages of using doxil
avoids non-specific tumour toxicity
extends circulation life
targeting of tumour can be enhanced by EPR
what is EPR
enhanced permeation and retention
poor quality ethelial lining of tumours allows liposomes to selectively enter tumours, lack of lymphatic system leads to retention
what are the issues with using doxorubicin in a liposome
nanoparticles can be detected as foreign bodies by MPS
what is MPS
mononuclear phagocyte system - removes foreign objects from blood stream
what are the maximum allowed doses of doxorubicin and doxil
rubicin - 60 mg/m2
doxil - 50 mg/m2
what conditions must ideally be met for dox-liposome manufacture
simple method with cheap materials
uniform liposome formation
100% trapping of drug
good release rate
how do lipids effect drug release and elimination
choice of lipid effects bilayer permeability
longer chain phospholipids release drug more slowly
what can be added to doxil to modify membrane permeablity
chloesterol
what are the 2 two approaches to adding doxorubicin into a liposome
active and passive
how does passive encapsulation work and what is a problem with this
hydrate lipid layers with aqueous doxorubicin
about 80% ends in liposome
some ends in bilayer
how does active encapsulation work
dried liposome is hydrated with an acid buffer (citrate)
external pH is increased
doxorubicin is deprotonated and enters liposome
it is then reprotonated
what is an alternative active encapsulation method
make liposomes with ammonium sulfate
replace exterior with same pH NaOH
ammonia in liposome leaves
dox-NH2 moves in and protonates
what is the main problem that is addressed by solid drug nanoparticles
oral drugs are preferred but many have poor:
solubility
bioavailability
permeation across key barriers
what are the 2 key barriers that are typically difficult to cross
blood brain barrier
gut blood barrier
what is bioavailablity
percentage of drug that enters the blood stream
what decides what can enter the blood from the gut
epithelial cells in the villi (small intestine)
describe drug uptake from gut to blood
active or passive
describe drug uptake from blood to gut and what is it called
reflux
active
why do nanoparticles strongly adhere to surfaces
have very high surface to volume ratio
what are the 2 approaches for making solid drug nanoparticles
bottom up and top down
what is the top down approach to making SDNs
homogenisation or nanomilling of large particles into smaller ones
what is the bottom up approach for making SDNs
nanoprecipitation or emulsion manipulation
what is nanomilling and what must be present in the process
grinding of large particles with solid beads
needs stabiliser present
what are the issues with attrition methods for making SDNs
breaking large particles makes new surfaces
if these are not stabilised the particles will aggregate
what can be used to stabilise newly broken SDNs
surfactants and polymers
what does the suitability of a stabiliser depend on
surface interactions
conc of polymer
balance of entropy loss and enthalpy gain
