Biologicals 2 Flashcards
For what reason would modifications be made to protein drugs?
Improve the stability, efficacy and pharmacokinetics
How can proteins be engineered?
Using recombinant DNA technology or chemical modification
What insulin modification does Humalog have?
Extra Lys and Pro added in 30 position
What insulin modification does NovoLog have?
Extra Asp in 30 position
What insulin modification does Lantus have?
Extra Gly in 20 position of a chain.
2 x extra Arg on end of B chain
What insulin modification does Levemir have?
Extra Lys on end of a chain
What benefits does the hydrophilicity of PEG bring?
Improved solubility
Reduced protein binding
Improved BA
Avoidance of phagocytosis
What benefits does the flexibility of PEG bring?
Shielding antigenic sites Reduced toxicity Proteolytic resistance Reduced clearance Improved thermal and mechanical stability
Why can PEGylation negatively affect protein activity?
Can block functional parts of the protein
What do polymer and lipid-based nanoparticles do?
Encapsulate proteins and ideally achieve intracellular delivery
How can nanoparticles be modified?
With shielding molecules and targeting ligands
What can we use for extended release of proteins?
Polymer matrices and microchips
Microchips can have wells containing what?
Lypholised protein or liquid formulation
What are the most widely used polymers for polymeric CDDS?
Hydrophobic and only soluble in organic solvent
What do we often need to generate to get the hydrophilic biological drug into the hydrophobic polymer?
Emulsions
