Carbon based DDS Flashcards
describe the structure of CNTs
strip of a graphene sheet rolled into a tube
depending on hm sheets, CNTs can be…
single layer
multiple layers of sheets
What 3 methods can be used to prepare carbon nanotubes?
Arc discharge
Chemical vapor deposition CVD
Laser ablation
what does arc discharge method use to create CNTs and name an advantage and disadvantage
graphite
perfect CNT
but ‘C’ contaminant and limited quantities
what does chemical vapor deposition (CVD) method use?
most common type
using hydrocarbon and metal catalysts
laser ablation technique uses what 2 things and produces what type of CNTs?
graphite + laser
SWNT
what are the 2 types of CNTs?
single-walled CNTs (SWNT) - one layer graphite
multi-walled CNTs (MWNT) - several graphite concentric layers
describe CNT properties
-structure
- mechanic properties…
ordered structure
extraordinary mechanical properties
electrostatic properties
metallic
semiconducting-insulating
what are the main issues with CNTs?
insoluble in any organic solvent or aqueous solution
as rlly hydrophobic
what is CNT functionalism?
addition of functional groups to CNTs
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
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
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
How are CNTs made biocomaptible?
dipolar cycloaddition reaction
What are the effects of covalent functionalisation of CNT? 3
Improved aqueous solubility + dispersibility
Improved individualisation.
Allows further modifications by electrostatic and covalent interaction.
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:)
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
OR
chemical functionalisation- use solvent to improve NT dispersibility in aq media
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
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)
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
what can SWNTs do?
enter the nucleus via nuclear pores
difference between the nanoneedle hypothesis and endocytosis mechanism of NT entering cell?
nanoneedle: spontaneous, no energy needed (independent)
endocytosis: needs energy
NTs can go into cells thus can be used as DDS (+ imaging) regardless of what 2 factors?
functional group
cell type
PK…
pharmacology = science that deals w origin, nature, chem, effects, uses of drugs and includes what 5 aspects?
pharmacognosy
PK
PD
P-therapeutics
toxicology
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
- pristine vs functionalised
- type of funcitonalisation: covalent/ non (coating)
- degree of functionalisation
- dispersibility of CNT
- 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
