Synthesis of Nanomedicines Flashcards

1
Q

what are the 2 categories of nanomedicines that will be focused on

A

solid drug nanoparticles

nanocarriers

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2
Q

what are polymers made up of

A

a chain of multiple monomers

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3
Q

what are the 2 ways of making polymers

A

chain growth

step growth

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4
Q

describe the process of chain growth

A

adding monomers to the end of the polymer chain

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5
Q

describe the process of step growth

A

using a monomer with 2 functional ends growth can occur in both directions

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6
Q

what type of monomers are used in chain growth

A

molecules with alkenes form the carbon backbone

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7
Q

what monomers are used for step growth of polymers

A

bifunctional molecules like amino acids

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8
Q

what is the degree of polymerisation

A

chain length (number of monomers in chain)

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9
Q

what is a polymer therapeutic

A

polymers where an active drug makes up more than 50% of the polymer

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10
Q

give an example of a therapeutic polymer and describe how the drug is released in the body

A

aspirin or morphine polymer

polymer is hydrolysed to yield drug

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11
Q

what is a dendrimer and how can it bind to pathogens

A

highly branched polymer

has many binding sites for pathogen to bind

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12
Q

how do polymer drug conjugates work

A

drug is bound to polymer backbone by spacer (PEG)

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13
Q

what advantages are there of using polymer drug conjugates and give an example

A

may reduce toxicity via enhanced permeation and retention

doxorubicin is an example

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14
Q

how are polymer micelles formed

A

PEGylation of drug to make drug surfactants

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15
Q

what can be added to aid amine conjugation

A

N-succinimidyl carbonate

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16
Q

how do polymers act as surfactants when bound to a drug

A

if drug is hydrophobic the polymer acts as the hydrophilic section and forms micelles above the CMC

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17
Q

how does the length of a polymer chain effect the activity of the chain ends

A

in longer chains the concentration of chain ends is lower

heavy polymers coil so the chain ends can be harder to find

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18
Q

how can gold nanoparticles be used as nanocarriers

A

can be stabilised by surface adsorbed molecules (PEG)
these can undergo exchange with drugs
exchange can be tuned

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19
Q

give an example of how gold nanoparticles as nanocarriers can be tuned

A

ligands can chelate with radioactive materials as part of radiotherapy

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20
Q

describe multifunctional AuNPs as radiotherapy

A

thioterminated antibodies target breast tumours
177Lu isotope on thiolated PEG
stabilised by thio-PEGs

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21
Q

how gold nanoshells be made

A

NH2 functionality given to Si NPs
AuNPs added
treated with AuCl4 and H2O2 to grow gold surface

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22
Q

how can goldnanoshell be used as an anticancer drug

A

if they accumulate in tumours they can be selectively heated and killed with rear-IR laser

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23
Q

what can be achieved by ring opening polymerisation

A

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

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24
Q

how can nonfunctionalized polymer surfactant be used

A

can form micelles that can contain hydrophobic drugs - doxorubicin

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25
Q

what can be achieved by mixing functionalised and nonfunctionalized polymers

A

mixed micelle is formed - properties can be tuned depending on polymer ratio

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26
Q

how can dialysis be used to assemble micelles

A

put polymer in good solvent within membrane
place membrane in water
solvent will exchange
fresh water is added and final organic solvent is removed

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27
Q

what property must a dialysis membrane have to form micelles

A

pores must be smaller than the molecular weight cut off (MWCO)

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28
Q

how can dendrimers be used as unimolecular micelles

A

has cavities within structure

can encapsulate hydrophobic drugs

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29
Q

what size are the droplets in nanoemulsions

A

10-100nm

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30
Q

describe the properties of a macroemulsion

A

> 1 micrometre
opaque
unstable

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31
Q

describe the stability of nanoemulsions

A

unstable

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32
Q

what are the droplet sizes in microemulsions

A

10-50nm

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33
Q

describe micro emulsions

A

stable emulsion

clear

34
Q

how can emulsions be stabilised

A

by surfactants

35
Q

what are solid lipid nanoparticles

A

similar to emulsion but with solid fat rather than droplets

36
Q

how can solid lipid nanoparticles be made

A

mix lipid with drug and a solvent
emulsify into water
evaporate off organic solvent
forms homogenised emulsion as solvent evaporation reduces droplet size

37
Q

what are some advantages of solid lipid nanoparticles

A

improved drug stability
control over drug release
lipids are biodegradable
relatively easy to scale

38
Q

what is the main issue with solid lipid nanoparticles

A

lipid can crystallise without encapsulating drug - poor loading

39
Q

what are 2 lab techniques that can be used to make solid lipid nanoparticles

A

homogenisation

ultrasonication

40
Q

what is homogenation

A

process of making nanoparticles by pushing macroemulsion through small gap at high pressure

41
Q

how can polymer nanoprecipitates be formed

A

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

42
Q

what factors effect the size of nanoprecipitates made

A
organic solvent and its conc
miscibility of the polymer
viscosity
temperature
rate of addition to antisolvent (water)
43
Q

what are liposomes made up of

A

unimers with 1 hydrophilic head and 2 hydrophobic tails

44
Q

how does the liposome bilayer form

A

interdigitation of hydrophobic tails

45
Q

how can both hydrophilic and hydrophobic molecules be encapsulated in liposomes

A

hydrophilic molecules can reside in the core

hydrophobic molecules can be stored in the bilayer

46
Q

what are some advantages of using liposomes

A

made of easily modifiable lipids
biodegradible
low immunoresponce
low toxicity

47
Q

what are the disadvantages of liposomes

A

hydrophobic layer is thin

can be hard to encapsulate hydrophilic molecules

48
Q

what are SUVs

A

small unilamellar vesicles <100nm

49
Q

what are LUVs

A

large unilamellar vesicles 100-1000nm

50
Q

what is a GUV

A

giant unilamellar vesicle

1-50 micrometres

51
Q

what is a MLV

A
multilamellar vesicle (1-50 micrometres) 
double bilayer
52
Q

what is MVV

A

multivesicular vesicles
liposomes in liposomes
1-50 micrometres

53
Q

how are liposomes produced

A
phospholipid dissolved in organic solvent
dried
rehydrated with water
gentle stirring produces MLVs
processing gives LUV/SUV
54
Q

give the properties of neat doxorubicin

A

highly toxic
administered as Cl salt
has 3 different pKa values
self assembles in water via pi stacking

55
Q

what are the advantages of using doxil

A

avoids non-specific tumour toxicity
extends circulation life
targeting of tumour can be enhanced by EPR

56
Q

what is EPR

A

enhanced permeation and retention
poor quality ethelial lining of tumours allows liposomes to selectively enter tumours, lack of lymphatic system leads to retention

57
Q

what are the issues with using doxorubicin in a liposome

A

nanoparticles can be detected as foreign bodies by MPS

58
Q

what is MPS

A

mononuclear phagocyte system - removes foreign objects from blood stream

59
Q

what are the maximum allowed doses of doxorubicin and doxil

A

rubicin - 60 mg/m2

doxil - 50 mg/m2

60
Q

what conditions must ideally be met for dox-liposome manufacture

A

simple method with cheap materials
uniform liposome formation
100% trapping of drug
good release rate

61
Q

how do lipids effect drug release and elimination

A

choice of lipid effects bilayer permeability

longer chain phospholipids release drug more slowly

62
Q

what can be added to doxil to modify membrane permeablity

A

chloesterol

63
Q

what are the 2 two approaches to adding doxorubicin into a liposome

A

active and passive

64
Q

how does passive encapsulation work and what is a problem with this

A

hydrate lipid layers with aqueous doxorubicin
about 80% ends in liposome
some ends in bilayer

65
Q

how does active encapsulation work

A

dried liposome is hydrated with an acid buffer (citrate)
external pH is increased
doxorubicin is deprotonated and enters liposome
it is then reprotonated

66
Q

what is an alternative active encapsulation method

A

make liposomes with ammonium sulfate
replace exterior with same pH NaOH
ammonia in liposome leaves
dox-NH2 moves in and protonates

67
Q

what is the main problem that is addressed by solid drug nanoparticles

A

oral drugs are preferred but many have poor:
solubility
bioavailability
permeation across key barriers

68
Q

what are the 2 key barriers that are typically difficult to cross

A

blood brain barrier

gut blood barrier

69
Q

what is bioavailablity

A

percentage of drug that enters the blood stream

70
Q

what decides what can enter the blood from the gut

A

epithelial cells in the villi (small intestine)

71
Q

describe drug uptake from gut to blood

A

active or passive

72
Q

describe drug uptake from blood to gut and what is it called

A

reflux

active

73
Q

why do nanoparticles strongly adhere to surfaces

A

have very high surface to volume ratio

74
Q

what are the 2 approaches for making solid drug nanoparticles

A

bottom up and top down

75
Q

what is the top down approach to making SDNs

A

homogenisation or nanomilling of large particles into smaller ones

76
Q

what is the bottom up approach for making SDNs

A

nanoprecipitation or emulsion manipulation

77
Q

what is nanomilling and what must be present in the process

A

grinding of large particles with solid beads

needs stabiliser present

78
Q

what are the issues with attrition methods for making SDNs

A

breaking large particles makes new surfaces

if these are not stabilised the particles will aggregate

79
Q

what can be used to stabilise newly broken SDNs

A

surfactants and polymers

80
Q

what does the suitability of a stabiliser depend on

A

surface interactions
conc of polymer
balance of entropy loss and enthalpy gain