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Drug Delivery 2 > Nanoparticles > Flashcards

Nanoparticles Flashcards

1
Q

RNA interference

A

siRNA
MiRNA

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2
Q

SiRNA

A

Therapeutic agent
Endonucleolytic cleavage
One mRNA target
Fully complementary

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3
Q

MiRNA

A

Partially complimentary
Targets 3’ untranslated region
Translational repression
Degradation of MRNA
Endonucleolytic cleavage
Therapeutic agent
Drug delivery
Multiple targets

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4
Q

SaRNA

A

Self-amplifying RNA

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5
Q

CRNA

A

Can also be used as a bio marker

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6
Q

Mechanism of action of mRNA vaccines

A

Inject mRNA
MRNA interacts with dendritic cells
Dendritic cells produce antigens
Dendritic cells interact with T-cells
Cell destruction

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7
Q

Biological barriers to mRNA therapeutics

A

Protein optimization
Nuclease degradation
Inflammatory response
Limited endothelial extravasation
Mononuclear phagocytosis and RES entrapment
Intratumoral pressure
Negatively charged lipid belayer of cell membrane
Endosomal escape

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8
Q

Degradation by endonucleases

A

Modified chemistry that can escape endonucleases

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9
Q

Negatively charged lipid belayer of cell membrane

A

Formulate into nanoparticle DDS

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10
Q

MRNA nanotechnology closes

A

Catatonic lipid lipoplexes
Ionizable lipid nanoparticles
Polymeric carriers
Peptide carriers
Alternative vehicles

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11
Q

Cationic lipoplexes

A

Using positively charged lipoplexes to cross the negatively charged cell membrane
DOTMA
DOTAP
DOGS

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12
Q

Ionizable lipid nanoparticles

A

Multiple degree of inputs
Deals with toxicity issues in different pHs
Formulated with PEG conjugated lipid and a helper lipid like DOPE and DOPC

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13
Q

Polymer nanoparticles

A

Most have a primary amine at hat is complexed with the RNA backbone
PEI, PEG, PBAE, CART
Toxic when positively charged

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14
Q

Delivery vehicle modifications

A

PKa: determines their endosomal escape capacity
Chain length and linger rigidity affect translation (C12-C14 is optimal)
Double bond enhance sphere formation (e.g. linoleyl chains)
PEG length
Targeting agents: liver targeting ligands (ASPGR, ApoE) and dendritic cell targeting ligands (mannose, dectins, langerins)

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15
Q

Effect of route of administration

A

Most mRNA doses are localized in the liver with any route of admin
IV injection leads to accumulation in liver and lymph nodes
Wide distribution of systemic admin can leaf to antigen specific T cell immune response
Route of admin affects the distribution and efficacy of mRNA therapy

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16
Q

Endosomal escape mechanisms

A

In the late endosome, the pH of the compartment drops, the ionizable lipid becomes charges and interact with the anionic lipids of the endosomal membrane, leading to hexagonal phase and membrane destabilization

17
Q

Microfluids based mixing of two solvents

A

Allow the combination of water and ethanol to encapsulate mRNA
>90% encapsulation efficiency

Drug Delivery 2 (8 decks)

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