Carbon based DDS Flashcards by X X

describe the structure of CNTs

strip of a graphene sheet rolled into a tube

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depending on hm sheets, CNTs can be…

single layer
multiple layers of sheets

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What 3 methods can be used to prepare carbon nanotubes?

Arc discharge
Chemical vapor deposition CVD
Laser ablation

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

graphite

perfect CNT
but ‘C’ contaminant and limited quantities

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

using hydrocarbon and metal catalysts

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

graphite + laser
SWNT

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what are the 2 types of CNTs?

single-walled CNTs (SWNT) - one layer graphite

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

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describe CNT properties
-structure
- mechanic properties…

ordered structure
extraordinary mechanical properties
electrostatic properties
metallic
semiconducting-insulating

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what are the main issues with CNTs?

insoluble in any organic solvent or aqueous solution
as rlly hydrophobic

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what is CNT functionalism?

addition of functional groups to CNTs

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why do we use CNT functionalism? 3

increase hydrophilicity to allow increase aqueous dispersion
stops aggregation of CNTs
`allows further modifications by electrostatic and covalent bonds

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what molecules may be added as functionalisation of CNTs?

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

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

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

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How are CNTs made biocomaptible?

dipolar cycloaddition reaction

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What are the effects of covalent functionalisation of CNT? 3

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

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

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

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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?

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

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

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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?

spontaneous

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Describe how a CNT binds and penetrates lipid bilayers

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

(salt bridges forming at sametime)

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what is the nanoneedle theory?

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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what can SWNTs do?

enter the nucleus via nuclear pores

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

nanoneedle: spontaneous, no energy needed (independent)

endocytosis: needs energy

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

functional group
cell type

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PK…

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

pharmacognosy
PK
PD
P-therapeutics
toxicology

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how can CNTs be used?

radiolabelling fluorescence intensity analysis

what is radio labelling used for?

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

why do you always need a chellating agent in radiolabelling?

it will hold radioactive material together

In what ways is CNT pharmacology investigated?

Imaging Urinary excretion

what type of imagine is done for CNTs?

whole body 1D dynamic SPECT

are NTs very well/ not very well individualised?

v well

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

urinary excretion TEM analysis of urine

how are CNTs excreted from the kidney?

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

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

in the glomerular capillaries in large bundles

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

pristine

example of functional CNT that will get excreted?

ammonium func NTs go through and pass :)

what type of CNTs are excreted faster?

highly functionalised CNTs

where will low func NTs accumulate?

liver + spleen

where will high func NTs accumulate?

urine, bladder

5 key things to consider in biology + pharmacology of CNT

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

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

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

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

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

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

True want this :)

What are the two main applications of CNTs?

Sensing Theranostic

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

sensing applications

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

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

Describe how CNTs were used in the delivery of doxorubicin

CNT backbone acts a platform for complex formation with doxorubicin.

Describe how CNTs were used in the delivery of doxorubicin

CNT backbone acts a platform for complex formation with doxorubicin.

What allows interaction between doxorubicin and CNTs?

pi-pi stacking

What was observed when using CNTs to deliver doxorubicin?

Enhances cytotoxicity :(

how can CNTs be used in fluorescence intensity analysis?

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

what is MTX?

an antimetabolite + antifolate drug

MTX MoA?

competitively + reversibly innhibits enz DHFR responsible for folic acid metabolism

what enz does MTX inhibit?

DHFR dihydrofolate reductase

what does folic acid do?

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

drawbacks of MTX?

cellular resistance low uptake hence low efficiency

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?

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

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

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

role of cytotoxicity assessment?

assess 3 diff things and looking at cell viability, survival

get time dependence release of MTX depending on what?

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

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

peptide

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

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

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

linkage to PEG

how may doxorubicin be used with CNT: anticancer molecule?

pi-pi stacking

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

chemical linkage

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

chemical linkage t: disulfide bonds c: ester bonds

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

strutcural. electronic properties :)

what more can CNT offer vs current DS? 2

internalisation in live cells that may avoid endosomal uptake high SA for template for diff mols at same time

what abt NTs makes them biocompatible?

sidewall functionalisation