nanomedicines Flashcards
how are nanomedicines/lysosomes prepared via passive encapsulation
- 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
what other components can be added to lysosomes
cholesterol PEG
what are LUVs
large uni-lamellar vesicles (100nm-1um)
what are SUVs
small uni-lamellar vesicles (25-100nm, single lipid bilayer
what are MLVs
multi-lamellar vesicles
why would you add cholesterol to nanomedicines
hydrophobic, reduces permeability and enhances drug retention
why would you add PEG to a nanomedicine
avoid MPS system - allows EPR effect
how would you remotely load a drug into a liposome
○ Preform liposome with a gradient (pH, ionic strength) ○ Drug travels up gradient or forms complex with components of the compartment
which kind of drugs would accumulate in the aqueous phase of liposomes
log P<1.7
which kind of drugs would accumulate in the lipid phase of liposomes
log P >5
what are the reasons for encapsulating actives in lipids
alter pharmacokinetic reservoir for sustained releaseprotection
how does the MPS work
liposomes interact with opsonin’sopsonised liposomes enter MPS build up in MPS allows for stead release into the blood
what is the MPS
mononuclear phagocytic system - eventually feeds back to bloodstream
what do opsonins do
mark foreign cells for phagocytosis
how can opsonisation be avoided
Surface modification - PEGylation, creates hydrophilic surfaces - repel opsonins
what happens to liposomes that are not opsonised
EPR effect
what is the EPR effect
Enhanced permeability and retention (EPR) effect - allows these drugs to accumulate at pathogenic sites
what are 4 applications of nanomedicines
myocet and doxil - doxrubicin abraxane - paclitaxel covid vaccines
what is myocet
- doxorubicin in Cholesterol liposomes - 1st line treatment for metastatic breast cancer- MPS accumulation
what is doxil
- doxorubicin with Liposomes contain PEG2 DSPE- Advanced ovarian cancer and Kaposi’s sarcoma- EPR effect allows it to accumulate in the tumour
what is abraxane
- 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
what are some safety concerns with nanomedicines
- toxicity- biodegradability - metabolism and excretion
how are drugs renally cleared
via urine
how are drugs hepatically cleared
via bile/faeces
which drugs are renally cleared
small enough to be filtered by glomerulus (<6-8nm
how does hepatic clearance affect the drug activity
longer in the body so more side effects
what are the two mechanisms of EPR
passive and active
what is passive targeting
deposition of nano-sized systems within the tumour is enhanced due to characteristics of the tumour, not present in normal cells
what is active targeting
deposition of nano-sized systems within the tumour microenvironment is enhanced by the use of cell-targeting moieties such as protein, peptides, DNA
how does the tumour environment allow for passive targeting
- 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
what are some issues with EPR
- Needs high specificity - only 0.7% of injected accumulates at desired area - EPR effect is highly heterogenous - changes over time of tumour development
how does the lymph system function normally
○ Maintain plasma volume, ○ Prevent increased tissue pressure, and; Permit passage of leukocytes à proper functioning of immune system
