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year 3 exam 1 > nanomedicines > Flashcards

nanomedicines Flashcards

1
Q

how are nanomedicines/lysosomes prepared via passive encapsulation

A
  • 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
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2
Q

what other components can be added to lysosomes

A

cholesterol PEG

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3
Q

what are LUVs

A

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

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4
Q

what are SUVs

A

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

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5
Q

what are MLVs

A

multi-lamellar vesicles

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6
Q

why would you add cholesterol to nanomedicines

A

hydrophobic, reduces permeability and enhances drug retention

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7
Q

why would you add PEG to a nanomedicine

A

avoid MPS system - allows EPR effect

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8
Q

how would you remotely load a drug into a liposome

A

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

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9
Q

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

A

log P<1.7

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10
Q

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

A

log P >5

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11
Q

what are the reasons for encapsulating actives in lipids

A

alter pharmacokinetic reservoir for sustained releaseprotection

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12
Q

how does the MPS work

A

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

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13
Q

what is the MPS

A

mononuclear phagocytic system - eventually feeds back to bloodstream

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14
Q

what do opsonins do

A

mark foreign cells for phagocytosis

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15
Q

how can opsonisation be avoided

A

Surface modification - PEGylation, creates hydrophilic surfaces - repel opsonins

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16
Q

what happens to liposomes that are not opsonised

A

EPR effect

17
Q

what is the EPR effect

A

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

18
Q

what are 4 applications of nanomedicines

A

myocet and doxil - doxrubicin abraxane - paclitaxel covid vaccines

19
Q

what is myocet

A
  • doxorubicin in Cholesterol liposomes - 1st line treatment for metastatic breast cancer- MPS accumulation
20
Q

what is doxil

A
  • doxorubicin with Liposomes contain PEG2 DSPE- Advanced ovarian cancer and Kaposi’s sarcoma- EPR effect allows it to accumulate in the tumour
21
Q

what is abraxane

A
  • 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
22
Q

what are some safety concerns with nanomedicines

A
  • toxicity- biodegradability - metabolism and excretion
23
Q

how are drugs renally cleared

A

via urine

24
Q

how are drugs hepatically cleared

A

via bile/faeces

25
Q

which drugs are renally cleared

A

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

26
Q

how does hepatic clearance affect the drug activity

A

longer in the body so more side effects

27
Q

what are the two mechanisms of EPR

A

passive and active

28
Q

what is passive targeting

A

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

29
Q

what is active targeting

A

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

30
Q

how does the tumour environment allow for passive targeting

A
  • 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
31
Q

what are some issues with EPR

A
  • Needs high specificity - only 0.7% of injected accumulates at desired area - EPR effect is highly heterogenous - changes over time of tumour development
32
Q

how does the lymph system function normally

A

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

year 3 exam 1 (44 decks)

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