Can CNS drug targeting be viewed as advanced drug delivery?
Yes; needs to pass BBB
What are categories of nanoparticulate systems?
- nanocapsule (encapsulated drug, reservoir)
- nanospheres (drug-polymer matrix)
T/F; Polymeric nanoparticles can only carry low MW substances.
False
- can deliver both low and high MW substances
- ex. genes, proteins
What are the advantages of nanoparticles?
- increased bioavailability
- protection from degradation
- specific targets
characteristics of tumor vasculature
- heterogeneous distribution
- larger in size
- high vascular density
- more permeable
- more leaky
What factor allows retention of NP in solid tumors?
- high vasculature
- production of vascular mediators
F
- bioavailability
- dose / AUC
How can you actively target a tumor?
- ligand-receptor
- antibody-antigen
How are NPs utilized in targeting cancer cells?
NP conjugated with tissue or cell-specific ligand
examples of ligands
- lectins
- carbohydrates
- transferrin
- folate
passive targeting
delivering drug at local site
What are vectors?
gene carrier used in gene therapy
Steps in gene therapy
- genetic material packaged in vector to be transferred
- vector enters cytoplasm
- gene from vector to nucleus
- gene integrated into cellular DNA (if need be)
- gene expressed
What are the categories used in gene therapy?
- viral
- non-viral
viral vectors
- part of viral genome replaced by therapeutic gene
- this gene taken up by target cells and expressed
examples that viral vectors were used for
- retrovirus
- adenovirus
- adeno-associated virus
- herpes simplex virus (HSV)
risks of viral vectors
- inflammation
- cellular / humoral immune response
What are the components of a non-viral vector?
- therapeutic gene
- gene expression system
- gene delivery system
plasmid-based vectors
non-viral
size of plasmid DNA
- huge polyanion
- 100-200 nm
Plasmid potency can be reduced by which factors?
- chemical instability
- enzymatic instability
- colloidal instability
- sequestered by immune system
- uptake / adsorption of non-target cells
What are the most commonly used synthetic gene carrier?
- cationic polymers
- lipids
What are advantages of using cationic polymers / lipids as a gene carrier?
they condense plasmids into small particles and protect them from degradation
Lipid-based gene delivery
- low efficiency
- pH sensitive
- fusogenic at acidic pH
- facilitate release of plasmid in endosome
