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Lab 3 > Carbon based DDS > Flashcards

Carbon based DDS Flashcards

1
Q

describe the structure of CNTs

A

strip of a graphene sheet rolled into a tube

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2
Q

depending on hm sheets, CNTs can be…

A

single layer
multiple layers of sheets

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3
Q

What 3 methods can be used to prepare carbon nanotubes?

A

Arc discharge
Chemical vapor deposition CVD
Laser ablation

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4
Q

what does arc discharge method use to create CNTs and name an advantage and disadvantage

A

graphite

perfect CNT
but ‘C’ contaminant and limited quantities

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5
Q

what does chemical vapor deposition (CVD) method use?
most common type

A

using hydrocarbon and metal catalysts

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6
Q

laser ablation technique uses what 2 things and produces what type of CNTs?

A

graphite + laser
SWNT

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7
Q

what are the 2 types of CNTs?

A

single-walled CNTs (SWNT) - one layer graphite

multi-walled CNTs (MWNT) - several graphite concentric layers

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8
Q

describe CNT properties
-structure
- mechanic properties…

A

ordered structure
extraordinary mechanical properties
electrostatic properties
metallic
semiconducting-insulating

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9
Q

what are the main issues with CNTs?

A

insoluble in any organic solvent or aqueous solution
as rlly hydrophobic

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10
Q

what is CNT functionalism?

A

addition of functional groups to CNTs

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11
Q

why do we use CNT functionalism? 3

A
  1. increase hydrophilicity to allow increase aqueous dispersion
  2. stops aggregation of CNTs
  3. `allows further modifications by electrostatic and covalent bonds
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12
Q

what molecules may be added as functionalisation of CNTs?

A

PEG/ PEO
lipids
ssDNA (wrap around)
add diff R groups
PPO - hydrophobic, want to bind hydrophobic surface

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13
Q

what is the difference between a covalent and non-covalent bond CNT?

A

covalent bonds- incorporated with the CNT structure
non-covalent bonds- coat the CNT

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14
Q

How are CNTs made biocomaptible?

A

dipolar cycloaddition reaction

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15
Q

What are the effects of covalent functionalisation of CNT? 3

A

Improved aqueous solubility + dispersibility
Improved individualisation.
Allows further modifications by electrostatic and covalent interaction.

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16
Q

ammonium, —NH2 can be incorporated covalently (into) CNT.
this can turn to NH3+.
whats good about this?

A

can do non-covalent electrostatic interactions bc NT surface can add polycyclic ring struc to it:)

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17
Q

CNTs = graphene sheet rolled into tube
depends on num of sheets (SWNT/MWNT) made through 3 processed into pristine NTs, NOT dispersed in aq/organic solvent.
then must functionalise them by doing what?

A

non-covalent func equivalent to coating NT surface w other mols to increase dispersibility
for use in biomedical application

OR

chemical functionalisation- use solvent to improve NT dispersibility in aq media

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18
Q

CNTs and cell biology…

for the binding + penetration of model CNT w lipid bilayers, in what fashion can insertion of a model functionalised hydrophobic nanotube into a biomembrane occur?

A

spontaneous

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19
Q

Describe how a CNT binds and penetrates lipid bilayers

A

Firstly binds parallel to membrane surface.
Then reorients to perpendicular in the layers.

(salt bridges forming at sametime)

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20
Q

what is the nanoneedle theory?

A

insertion of a functionalised hydrophobic nanotube into a membrane spontaneously (no energy needed)
pierced in.

parallel CNT into a perpendicular CNT

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21
Q

what can SWNTs do?

A

enter the nucleus via nuclear pores

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22
Q

difference between the nanoneedle hypothesis and endocytosis mechanism of NT entering cell?

A

nanoneedle: spontaneous, no energy needed (independent)

endocytosis: needs energy

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23
Q

NTs can go into cells thus can be used as DDS (+ imaging) regardless of what 2 factors?

A

functional group
cell type

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24
Q

PK…

pharmacology = science that deals w origin, nature, chem, effects, uses of drugs and includes what 5 aspects?

A

pharmacognosy
PK
PD
P-therapeutics
toxicology

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25
Q

how can CNTs be used?

A

radiolabelling
fluorescence intensity analysis

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26
Q

what is radio labelling used for?

A

allows visualisation of CNT uptake for CT imaging, track where it goes

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27
Q

why do you always need a chellating agent in radiolabelling?

A

it will hold radioactive material together

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28
Q

In what ways is CNT pharmacology investigated?

A

Imaging
Urinary excretion

29
Q

what type of imagine is done for CNTs?

A

whole body 1D dynamic SPECT

30
Q

are NTs very well/ not very well individualised?

A

v well

31
Q

how are CNTs removed from the body?
+ hows this then quantified and presence of CNTs confirmed?

A

urinary excretion
TEM analysis of urine

32
Q

how are CNTs excreted from the kidney?

A

functionalised CNTs stop aggregation

aggregated non functionalised CNTs are too big = can’t fit the pores and cannot be excreted

33
Q

urinary excretion mechanism- where will non-functionalised MWNT be found (as too big for excretion)

A

in the glomerular capillaries in large bundles

34
Q

example of non-functional, big aggregate CNT that doesn’t get excreted?

A

pristine

35
Q

example of functional CNT that will get excreted?

A

ammonium func NTs go through and pass :)

36
Q

what type of CNTs are excreted faster?

A

highly functionalised CNTs

37
Q

where will low func NTs accumulate?

A

liver + spleen

38
Q

where will high func NTs accumulate?

A

urine, bladder

39
Q

5 key things to consider in biology + pharmacology of CNT

A
  1. pristine vs functionalised
  2. type of funcitonalisation: covalent/ non (coating)
  3. degree of functionalisation
  4. dispersibility of CNT
  5. individualisation vs aggregation
40
Q

in what case may NT non-covalent coating be removed and end up with aggregates?

A

if something not bound strongly to NT and injected IM, have other serum proteins + albumin trying to compete w NT surface…

41
Q

good to have high dispersibility of NTs but whats the problem?

A

will have competition of proteins wanting to go to surface of NTs = removes actual coating on surface :(

42
Q

HIGH func = HIGH CNT dispersibility = HIGH individualisation, meaning will go into excretion, and cells
T/F?

A

True

want this :)

43
Q

What are the two main applications of CNTs?

A

Sensing
Theranostic

44
Q

sensing or theranostic applications = SWNT: DNA biosensors, O2 -> DNA conformation changes.
eg meets a particular molecule + thats meant to change conformation

A

sensing applications

45
Q

for theranosticapplications, what sort of moieties may be attached to CNT surface?

A

MAB (for therapeutic + targeting)
single chain fragment
radioactive/ optical probe
anticancer drugs
hyperthermia

46
Q

Describe how CNTs were used in the delivery of doxorubicin

A

CNT backbone acts a platform for complex formation with doxorubicin.

46
Q

Describe how CNTs were used in the delivery of doxorubicin

A

CNT backbone acts a platform for complex formation with doxorubicin.

47
Q

What allows interaction between doxorubicin and CNTs?

A

pi-pi stacking

48
Q

What was observed when using CNTs to deliver doxorubicin?

A

Enhances cytotoxicity :(

49
Q

how can CNTs be used in fluorescence intensity analysis?

A

by detecting the pi-pi interactions between chromophores and CNT surface= larger AUC

50
Q

what is MTX?

A

an antimetabolite + antifolate drug

51
Q

MTX MoA?

A

competitively + reversibly innhibits enz DHFR responsible for folic acid metabolism

52
Q

what enz does MTX inhibit?

A

DHFR
dihydrofolate reductase

53
Q

what does folic acid do?

A

synthesis of nuceloside Thymidine req for DNA synthesis + Purine base synthesis

54
Q

drawbacks of MTX?

A

cellular resistance
low uptake
hence low efficiency

55
Q

expect MTX to enter cekks via folic acid receptors (receptor mediated endocytosis)
enter form surface of NT via nanoneedle hypothesis

what was the issue with this?

A

MTX was rlly stuck into NT + no delivery of MTX w NT compared to MTX alone

56
Q

role of esterases in cells after CNT-linker-MTX administered?

A

will cleave linkers off, inc conc of MTX in cells ==> will inhibit enz + DNA synthesis :)

57
Q

role of cytotoxicity assessment?

A

assess 3 diff things and looking at cell viability, survival

58
Q

get time dependence release of MTX depending on what?

A

the linker used
(as cleavable linkers showed to be active compared to MWNT-MTX without linker)

59
Q

what type of linker with MTX had better potency than MTX alone?

A

peptide

60
Q

when looking at siRNA complexes, how will using CNT and liposome be different?

A

CNT- go straight into cytoplasm, no endosomes- dont worry about pH reduction/ degradation of material

liposome - must design pH sensitive + ensure siRNA will be released/ if using normal liposome, worry abt siRNA degradation in endosome

61
Q

how may Pt(IV) and paclitaxel be used with CNT: anticancer molecule?

A

linkage to PEG

62
Q

how may doxorubicin be used with CNT: anticancer molecule?

A

pi-pi stacking

63
Q

how may MTX and cisplatin be used with CNT: anticancer molecule?

A

chemical linkage

64
Q

how may taxoid and camptothecin be used with CNT: anticancer molecule?

A

chemical linkage

t: disulfide bonds
c: ester bonds

65
Q

what features of CNTs may be used in biomedicine and what features are particularly attractive?

A

strutcural.
electronic properties :)

66
Q

what more can CNT offer vs current DS? 2

A

internalisation in live cells that may avoid endosomal uptake

high SA for template for diff mols at same time

67
Q

what abt NTs makes them biocompatible?

A

sidewall functionalisation

Lab 3 (21 decks)

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