Term
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Definition
controlled
site-specific drug delivery (SSDD) |
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Term
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Definition
drugs with short half life
undesirable distribution of drug (little at target and too much at non-target organs, more S/E)
poor drug transportation across biological membrane
low therapeutic index (poor solubility, stability, absorption) |
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Term
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Definition
biocompatible
biodegradable
CR to achieve effect
prevent degradation or inactivation of drug during transit to target site
maintain drug carrier integrity
target recognition
enhance therapeutic index of drug |
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Term
| classification of drug targeting |
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Definition
1st order: vascular compartment (anticancer to organ)
2nd order: cellular (tumour cells vs normal cells)
3rd order: intracellular (lysosomes) highest level |
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Term
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Definition
| utilises natural disposition pattern of carrier systems (drug in lysosomes) |
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Term
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Definition
| uses homing device or principle to change the natural disposition pattern of the carrier to selectively target one particular tissue or cell type (high level of targeting) |
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Term
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Definition
access to the site
retention at target site
timing of drug release at the target site |
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Term
| biological process involved in drug targeting? |
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Definition
| drug or delivery system-blood circulation-extravasation-target site (extravascular) |
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Term
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Definition
sml MW: can diffuse thru capillary wall
lge MW: in lymph |
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Term
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Definition
continuous: 20nm (blood brain barrier) very narrow
fenestrated: 20-80nm (liver)
sinusoidal: up to 150nm (liver and spleen)
both fenestrated and sinusoidal tissue can occur in diseased tissue |
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Term
| factors affecting extravasation: |
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Definition
| physiochemical properties like molecular size, shape, charge, lipophilicity |
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Term
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Definition
macromolecule (soluble): thru pinocytosis, inter-endothelia junctions & gaps in capillary structure
receptor mediated transport systems (if Mw >70Da retained in circulation (increase MRT)
colloidal: escape thru gaps in fenestrated and sinusoidal
thru phagocytes
via receptor mediated (if nano) |
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Term
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Definition
internalisation of cell membrane by:
phagocytosis (cell eating engulfment of particulate matter)
pinocytosis: (cell drinking fluid) |
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Term
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Definition
| recognition-adhesion-opsonisation(attacks cell in phagocytosis)-internalisation and digestion or oponisation (recognise foreign paricles)-engulfing |
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Term
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Definition
sml molecule goes thru extravastion
Lge molecules goes thru lymphatic vessel (interstitial sites).
tumour can lack lymphatic vessel and therefore no EPR: (enhanced permeability and retention) |
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Term
| components for carrier-based targeted drug delivery |
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Definition
an active moiety (drug)
a carrier (polymer or macromolecule)
a homing device |
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Term
| 4 classification of drug carriers: |
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Definition
soluble macromolecular
micellar, or self-assembling
dendrimers
colloidal carriers (liposomes, nano/microparticles) |
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Term
| soluble macromolecular drug carriers |
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Definition
soluble and move freely around the body
uptake by pinocytosis
alter pk of drug
distribution and elimination depend on: MW, hydro/lipophilicity, ionic nature, interaction with surrondings
Human cells are -ver |
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Term
| problems with macro and antibodies: |
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Definition
loss of activity
low drug carrying capacity
poor diffusion,
immunogenicity
loss of specificity |
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Term
| barrier for tumour targeting via AB: |
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Definition
tumour heterogeneity
antigen shedding and modulation
Tumour antigens aren't necessarily unique |
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Term
| overcoming tumour barriers to AB: |
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Definition
use different monoclonal AB
antigen that don't shed or modulate
release drug before antigen conjugate complex is endocytosed
inject free MAb prior |
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Term
| other ligands for tumour targeting |
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Definition
endogenous ligands: transferrin (overexpressed)
folic acid
interleukins (immunological ligands) |
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Term
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Definition
sml
polymeric micelles hydrophilic-hydrophobic-hydrophilic with the drug solubilised to the hydrophilic-hydrophobic bond
50-150nm
penetrate fenestrated and sinusoidal due to EPR effect
self assemble and allow chem modification on surface
entrap drug and in the core or bond to copolymer (needs hydrolysis) release via diffusion or enz cleavage
able o attach ligands on surface |
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Term
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Definition
made by polymers 1-100um
highly branched
terminal groups can be modified
amphipathic dendrimer can put multiple things onto them like:
solubilising groups
targeting moiety
attached drug |
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Term
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Definition
unilamellar or multilameller vesicle
habe a lipid bi layer (non polar tail?polar head) protect the drug
vehicle for poor solubility (lipophilic drugs)
alter PK of drug to reduce toxicity and increase effect |
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Term
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Definition
lipid bilayer
aqueous core
self assemble using phospholipid DSPC (phosphatidylcholine (polar head group)
(glycerol bridge)
(steric acid chain non polar tail) |
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Term
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Definition
HDL can attach and destroy it
Opsonin can attach then oponisation (uptake by MPS) and removed |
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Term
| liposome interaction with cells |
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Definition
fusion with cell membrane
adsorption to cell wall
endocytosis of liposomes by cell |
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Term
| steric stabilisation (stealth tech) |
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Definition
grafting hydrophilic flexible polymer like PEG MW (1000-5000) on the lipid bilayer
prolong circulation and reduce recognition by MPS and HDL
eg DOXIL increase action and decease S/E using MPEG/DSPE
HSPC (phosphatidycholine)
histidine: buffer |
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Term
| Liposomes passive targeting |
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Definition
eg. amphotericin B, selectively target by uptake via MPS and taken to the liver and spleen (main site of systemic fungal infections)
passive cancer chemo:
EPR
phagocytosis of liposomes by monocytes
prolonged circulation (doxil) |
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Term
| liposome and extravasation via hyperthermia? |
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Definition
| this can open the gaps in y tumours, with tumour vasculature gaps usually bigger |
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Term
| liposome active targeting |
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Definition
| immunoliposome: attached monoclonal antibody (FAB region) using DTT as the anchoring molecule |
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Term
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Definition
biodegradable
biological inert
versatile
hydrophilic and hydrophobic drugs
protect entrapped drug
reduce toxicity
passive or active targeting
prolong half life and effect |
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Term
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Definition
clearance via MPS
low drug loading
poorly control release of drug
stability problems (lipid stability and drug leakage)
size is variable |
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Term
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Definition
ambisone (amphotericin B powder)
depotcyte (cytarabine) multivesicular lipid particles
daunoxome (daunorubicin)liposomal dispersion
doxil (doxorubicin) PEG stealth liposome |
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Term
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Definition
follow instructions
not with NaCl or other electrolytes or preservative unless it says to
store admixtures 2-8 and within 24hrs
no filter should be used
never freeze because water forms crystals and damage the bilayer |
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Term
| nanoparticle and microparticles: |
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Definition
nano: 10-1000nm (ideal <300 and extravastate <150)
micro: 0.5-100um (<100um capillary embolise)
from natural or synthetic particles |
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Term
| factors affecting drug delivery? |
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Definition
size of particle (for circulation and SA)
surface characteristics of paricles (hydrophilic or hydrophobic hydrophobic is quicker removed)
biogradable is less toxic and less accumulation
drug release profile and drug loading required
interaction between matrix (other ingredients in carrier system) materials and drug (ion interaction prolong release) if no interacting drug released quicker
interaction between the carrier and targets (direct the drug to target) |
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Term
| influence to performance of particulate drug delivery systems: |
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Definition
pathological nature and conditions, eg tumour can lack EPR, tumour have heterogeneous nature with blood flow and lymphatic drainage
brain tumour drug needs to cross BBB
active targeting with ligands that can be upregulated in tumours (peptide RGD)
influence of external stimuli: like temp, magnetic field, light, ultrasound |
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Term
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Definition
<0.05um: liver, spleen, BM, tumours there via extravasation
0.1-2um: liver, spleen, BM via MPS or ES
2-12um: lung, liver, spleen via >7um capillary embolization
>12um: accumulation in lung via capillary embolisation |
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Term
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Definition
| injection of drug bearing MP >10um for in siu release via selective arterial catheterization |
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Term
| active targeting of NP & MP |
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Definition
attach AB or cell specific ligands on surface of NP with or without stealth stabilisation
magnetically controlled drug release MP & NP: use Fe3O4 and control with external magnetic field to site
co-administration of vasoconstrictor (MP) |
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Term
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Definition
size
type of matrix material/wall
stability of particles
drug loading
drug binding mechanisms and localisation |
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Term
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Definition
dissolution, diffusion, de-sorption
ion-exchange
rerosion or enz degradation of matrix |
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Term
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Definition
is for breast cancer
albumin bound form of paclitaxel np 130nm
short infusion time
no IV needed
no premeds needed |
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Term
| features of MP/NP carriers |
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Definition
distribution is non-uniform and size and targeting ligand dependent
extravasation limited to <150nm
no specific target ligand can only be taken up by the MPS
MP >10um can be for chemoembolization
drug loading better for potent drugs
they protect drugs from chemical and enz degradation and can provide SR
never overlook toxicity |
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