College aantekeningen
Nanomedicine notes
- Instelling
- Radboud Universiteit Nijmegen (RU)
Detailed notes on all of the lectures including many pictures
[Meer zien]Voorbeeld 3 van de 16 pagina's
Voorbeeld 3 van de 16 pagina's
In winkelwagengesponsord bericht van onze partner
Verkoper
Volgen
Voorbeeld van de inhoud
DRUG DELIVERY STRATEGIESNANOMEDICINE
− enhance the concentration of the drug molecule at its place of action:
o to avoid side effects
o to use expensive drugs more effectively → less total dose and higher concentration for a
longer period of time (protection from degradation and excretion)
o for an established drug molecule (e. g. doxorubicin)
o for a molecule that otherwise could not be a drug (e. g. siRNA)
− requirements:
o ability to synthesize and manipulate molecules → (bio-)chemistry
o structural and functional understanding of biology at nanoscales → microscopy/structure
analysis
o control of localization → delivery/targeting strategies
o generation of small structures → semiconductor technology/principles of molecular self-
organisation
− size:
o 80 - 200 nm
o too small → problems with endocytosis
o too big → only phagocytosis possible which not all cells are capable of
DRUG DELIVERY
− classical drugs:
o small organic molecules
o lipophilic enough to cross membranes (compatible with oral delivery)
o distribute mostly freely throughout the body
o act by inhibiting enzymes/receptors
− what is needed:
o protection from degradation,
o modifying pharmacokinetics → long circulation time
o tissue/cell targeting → decrease of side-effects, avoidance of drug resistance
− requirements:
o minimal design to implement main functionalities → as simple as possible to make it in large
scale)
o toxicity
o stability → secretion vs. break-down
o compatibility with drugs → hydrophilicity
o protective matrix
o production costs
o intracellular trafficking (in only a few cases)
o targeting functionality
,− delivery routes:
BARRIERS
− the more barriers can be
crossed the more
comfortable route of
application → pill vs.
injection
− organ-dependent:
o continuous capillaries – skeletal muscle vs. blood-brain barrier → many vs. few transport
vesicles
o fenestrated capillaries – endocrine glands, intestines, pancreas, kidneys
o sinusoid capillaries – bone marrow, lymph nodes, liver, spleen
− cellular barriers:
o for non-destructive transport, there is no permeation enhancement without activation of
intracellular processes
o paracellular:
o tight junction proteins interacting with each other → controlling the tightness of the
junction
o Ca2+ signals induced → change in the protein conformation → less sticky proteins
o permeation enhancers → not an option for nanomedicine (too large)
o transcellular:
o cell surface receptors
, o conjugation of a drug to a metabolic cargo (vitamin B12) which binds to the receptor
o hijacking a transport system
− blood-brain-barrier:
o coupling the medicine to a
liposome which binds to the
transferrin receptor (TfR), human
insulin receptor (HIR) or LRP →
transcytosis
o can lead to less transferrin
import → side effects
o the affinity of the targeting
ligand must not be too high →
otherwise no release and no
transcytosis
TARGETING STRATEGIES
− tissue/cell-specific ligands: antibodies, Fab, single chain antibodies, peptides, small molecule ligands
− environment-dependent enrichment – pH, enzymatic activities
− tissue structure – EPR effect
− EPR effect
o enhanced permeation and retention in tumours
o molecules tend to accumulate more in tumour tissue rather than normal tissue
o result of rapid vascularization
o absence of lymphatic drainage does not promote extravasation (fluid leakage) → only
transport through diffusion (inefficient)
− active targeting:
o a receptor binding the drug
o antibody targeting the drug to the tumour
o randomly diffusing through the tumour, but higher retention
− drug delivery vehicles:
o nanoparticles – lipid and polymer based
o conjugates – antibodies and receptor ligands
− liposomes:
o aqueous core with a membrane bilayer coat
o passive targeting
o doxorubicin: used for chemotherapy, greatly enhanced plasma half-life, high peak
concentrations can be avoided reducing cardiotoxicity, however, it can’t reach tumour cells
while in a liposome (almost nothing is released into the cell)
o advantages:
o increased efficacy, therapeutic index, and stability of the encapsulated drug
o avoidance of side effects/toxicity
o improved pharmacokinetics due to slower release
o high flexibility
Voordelen van het kopen van samenvattingen bij Stuvia op een rij:
Verzekerd van kwaliteit door reviews
Stuvia-klanten hebben meer dan 700.000 samenvattingen beoordeeld. Zo weet je zeker dat je de beste documenten koopt!
Snel en makkelijk kopen
Je betaalt supersnel en eenmalig met iDeal, creditcard of Stuvia-tegoed voor de samenvatting. Zonder lidmaatschap.
Focus op de essentie
Samenvattingen worden geschreven voor en door anderen. Daarom zijn de samenvattingen altijd betrouwbaar en actueel. Zo kom je snel tot de kern!
Veelgestelde vragen
Wat krijg ik als ik dit document koop?
Je krijgt een PDF, die direct beschikbaar is na je aankoop. Het gekochte document is altijd, overal en oneindig toegankelijk via je profiel.
Tevredenheidsgarantie: hoe werkt dat?
Onze tevredenheidsgarantie zorgt ervoor dat je altijd een studiedocument vindt dat goed bij je past. Je vult een formulier in en onze klantenservice regelt de rest.
Van wie koop ik deze samenvatting?
Stuvia is een marktplaats, je koop dit document dus niet van ons, maar van verkoper ninajunakovi. Stuvia faciliteert de betaling aan de verkoper.
Zit ik meteen vast aan een abonnement?
Nee, je koopt alleen deze samenvatting voor €6,69. Je zit daarna nergens aan vast.
Is Stuvia te vertrouwen?
4,6 sterren op Google & Trustpilot (+1000 reviews)
Afgelopen 30 dagen zijn er 53340 samenvattingen verkocht
Opgericht in 2010, al 14 jaar dé plek om samenvattingen te kopen