nanomedicines

Question 1

how are nanomedicines/lysosomes prepared via passive encapsulation

Answer 1

• Lipids added to organic solvent and freeze dried (drug added here if lipophilic) - Lipid cake formed - Aqueous solution added (with drug is lipophobic) - Hydrated, mixed and agitated to form multilamellar vesicles - Sonication/extrusion/homogenisation to break them down

Question 2

what other components can be added to lysosomes

Answer 2

cholesterol PEG

Question 3

what are LUVs

Answer 3

large uni-lamellar vesicles (100nm-1um)

Question 4

what are SUVs

Answer 4

small uni-lamellar vesicles (25-100nm, single lipid bilayer

Question 5

what are MLVs

Answer 5

multi-lamellar vesicles

Question 6

why would you add cholesterol to nanomedicines

Answer 6

hydrophobic, reduces permeability and enhances drug retention

Question 7

why would you add PEG to a nanomedicine

Answer 7

avoid MPS system - allows EPR effect

Question 8

how would you remotely load a drug into a liposome

Answer 8

○ Preform liposome with a gradient (pH, ionic strength) ○ Drug travels up gradient or forms complex with components of the compartment

Question 9

which kind of drugs would accumulate in the aqueous phase of liposomes

Answer 9

log P<1.7

Question 10

which kind of drugs would accumulate in the lipid phase of liposomes

Answer 10

log P >5

Question 11

what are the reasons for encapsulating actives in lipids

Answer 11

alter pharmacokinetic reservoir for sustained releaseprotection

Question 12

how does the MPS work

Answer 12

liposomes interact with opsonin’sopsonised liposomes enter MPS build up in MPS allows for stead release into the blood

Question 13

what is the MPS

Answer 13

mononuclear phagocytic system - eventually feeds back to bloodstream

Question 14

what do opsonins do

Answer 14

mark foreign cells for phagocytosis

Question 15

how can opsonisation be avoided

Answer 15

Surface modification - PEGylation, creates hydrophilic surfaces - repel opsonins

Question 16

what happens to liposomes that are not opsonised

Answer 16

EPR effect

Question 17

what is the EPR effect

Answer 17

Enhanced permeability and retention (EPR) effect - allows these drugs to accumulate at pathogenic sites

Question 18

what are 4 applications of nanomedicines

Answer 18

myocet and doxil - doxrubicin abraxane - paclitaxel covid vaccines

Question 19

what is myocet

Answer 19

• doxorubicin in Cholesterol liposomes - 1st line treatment for metastatic breast cancer- MPS accumulation

Question 20

what is doxil

Answer 20

• doxorubicin with Liposomes contain PEG2 DSPE- Advanced ovarian cancer and Kaposi’s sarcoma- EPR effect allows it to accumulate in the tumour

Question 21

what is abraxane

Answer 21

• paclitaxel used for Breast cancer and non-small cell lung cancer - Binds to albumin in blood, so no need for PEGylation * Hydrophobic drug, hydrophilic albumin - EPR effect

Question 22

what are some safety concerns with nanomedicines

Answer 22

• toxicity- biodegradability - metabolism and excretion

Question 23

how are drugs renally cleared

Answer 23

via urine

Question 24

how are drugs hepatically cleared

Answer 24

via bile/faeces

Question 25

which drugs are renally cleared

Answer 25

small enough to be filtered by glomerulus (<6-8nm

Question 26

how does hepatic clearance affect the drug activity

Answer 26

longer in the body so more side effects

Question 27

what are the two mechanisms of EPR

Answer 27

passive and active

Question 28

what is passive targeting

Answer 28

deposition of nano-sized systems within the tumour is enhanced due to characteristics of the tumour, not present in normal cells

Question 29

what is active targeting

Answer 29

deposition of nano-sized systems within the tumour microenvironment is enhanced by the use of cell-targeting moieties such as protein, peptides, DNA

Question 30

how does the tumour environment allow for passive targeting

Answer 30

- Rapid, invasive growth - High cell numbers in a confined space - Angiogenesis § Metabolic demand increased - pro-angiogenic factor release - Lymph damaged at tumour site, less drug removal

Question 31

what are some issues with EPR

Answer 31

- Needs high specificity - only 0.7% of injected accumulates at desired area - EPR effect is highly heterogenous - changes over time of tumour development

Question 32

how does the lymph system function normally

Answer 32

○ Maintain plasma volume, ○ Prevent increased tissue pressure, and; Permit passage of leukocytes à proper functioning of immune system