Pharmacodynamics & -kinetics
12 important questions on Pharmacodynamics & -kinetics
What is a liposome and which liposomes are there?
- SUV = small unilamellar vesicles
- LUV = large unilamellar vesicles --> most room for hydrophylic drugs
- MLV = multilamellar vesicles --> most room for hydrophobic drugs
- MVV = multivesicular vesicles
What are the properties of liposomes?
Explain the liposome loading methods
- Passive: drug is added during formulation of the liposomes
- Dehydration-rehydration: post-formulation loading in which empty liposomes are freeze-dried in presence of the drug and later rehydrated with water.
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What are the pro's and con's for crystal-structures in liposomes?
con - slow release (needs to be dissolved first), delayed bioavailability.
What is the EPR effect?
The core of a tumor becomes anoxic --> more vessel growth --> rapid growth results in less organization --> endothelium will become leaky --> liposomes get only into the tumor environment, not in normal tissue
- limitation 1: poor lymphatic system functioning in tumors --> more fluid present --> more pressure --> liposomes enter tumor tissue less easily
- limitation 2: unspecific targeting to the liver also occurs (RES system).
What are the pros and cons of PLGA
Cons: concern of denaturation for protein drugs, burst release, loading is drug depending.
In which way have oligonucleotides an enormous therapeutic potential?
siRNA = selective downregulation of gene expression
mRNA = transient expression of therapeutic proteins, vaccination
DNA = gene therapy, vaccination
What is the function of cell-penetrating peptides (CPP)?
- 8-30 amino acids in length
- positive charge (mostly arginine (R) rich)
- Receptor-independent endocytosis/translocation
- Examples: R9, TAT, Penetratin, TP10
- Used for: drugs, proteins, particles, oligonucleotides, DNA, RNA translocation
- Pros: biodegradable, well-accessible, less toxicity.
Explain the concept of bystander killing
- works against heterogeneity of the tumor (cells who do not express the receptors and otherwise would evade the killing)
- kills other cell types (e.g. Fibroblasts) which would otherwise support the tumor growth.
What are the steps of endosomal release?
- Binding to the cell surface
- endocytosis
- endosomal release
- replication, mRNA synthesis
- protein synthesis
- virus budding
What is the proton sponge effect?
What are Lipinski's rule of 5?
--> only predicts passive intestinal absorption (lipophilic compounts are removed by the liver).
- HBD <5
- HBA <10
- Molecular weight <500 Da
- LogP <5
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