Hydrogel Drug Deliver Systems (G3) Flashcards
Goran lecture 3 of 6
What exactly is a hydrogel?
3D structures composed of cross linked hydrophilic polymers that are insoluble but able to swell rapidly taking up lots of water and biological fluids
What are microgels?
- Spherical hydrogel particles
How do we synthesise hydrogels from monomers?
- Hydrogels are chains of polymers that have been crosslinked so that they are not soluble in water
- Monomer (HEMA)
- Crosslinker (EGDA)
- Crosslinked polymer (PHEMA)
Synthesis of hydrogels from polymers involves crosslinking hydrophilic polymers, what are the 2 methods of doing this?
- Chemical cross linking
- Physical cross linking
Describe the 3 methods of chemical crosslinking to synthesise hydrogel from polymers
1) Reacting an aldehyde and amine to form a schiff base hydrogel
2) reacting an aldehyde and diol to form an acetal
3) Oxidative coupling of phenol with hydrogen peroxide
What different forms of physical crosslinks are there? (5)
- Helix coil cross linking
- Hydrophobic interactions
- Charge interactions (iontropic gelation)
- Hydrogen bonding interactions
- Stereocomplexation
How does coil to helix cross linking occur to produce hydrogels from single polymer strands
1) At high temperatures the polymers are an aqueous solution in single strands
2) Upon cooling they begin to coil and intertwine forming a lattice of helices
Name 2 polymers that form natural helices when cooled
- gelatine
- agarose (used for media)
Explain how hydrophobic interactions can cause physical crosslinking to produce a hydrogel
- Polymers with both hydrophobic and hydrophilic tails exist in solution
- When temperature is increased, the hydrophobic tails of the polymer strands aggregate together forming clumps to minimise their contact with water
- This forms an insoluble lattice of polymer chains in bonded by the hydrophobic tails
What is another name for the process by which hydrophobic tails aggregate to form a hydrogel?
- Reverse thermal gelation
Explain the process of ionotropic gelation also known as charge interaction cross linking
- A reversible gelation process
- Crosslinking is brought about by the introduction of an oppositely charged polymer or a small molecule that is oppositely charged and acts like a crosslinker
What is unique to charge interaction cross linking?
- This crosslinking process is reversible
- Decross linking can be triggered by pH changes or adding monovalent ions that bins to the crosslinking molecules making them neutrally charged
Give an example of a hydrogel that is formed from charge interaction cross linking and explain it briefly
- Alginate polymers + CaCl2
- Ca2+ become the small charged particles that cross link the negatively charged COO- groups in the alginate
Explain how the process of fabrication of microgels by centrifugal extrusion through a nozzle works
1) A monomer solution designed to form microgels is loaded into the spinning chamber, with a specifically designed nozzle outlet.
2) The chamber spins, creating centrifugal forces that push the monomer solution through the nozzle, forming droplets.
3) The droplets land in a solution containing a crosslinking agent, that stabilises the droplets transforming them into microgel particles
In the process of fabrication of microgels by centrifugal extrusion through a nozzle, what parameters can effect the size and quality of the microgel particles?
- RPM/Speed of centrifuge
- Design of the nozzle
- monomer solution (concentration, type)
- Crosslinking agent solution (“)
How can the hydrogen bonds in microgels be broken and reformed into more specific shapes?
- Through shear forces, like being forced through a needle
- The hydrogen bonds break under shear forces and reform into microgel droplets through injection
What is stereocomplexation?
This is the formation of a complex molecule, structured by the association of two enantiomeric polymers, forming a complex with higher order and thus stable properties.
Give an example of a stereocomplex and its precursor molecules
PLA has two enantiomeric forms: poly(L-lactic acid) (PLLA) and poly(D-lactic acid) (PDLA). When PLLA and PDLA chains are mixed, they can associate through intermolecular forces such as hydrogen bonding, creating a stereocomplex
How does Glytaraldehyde chemically cross link Ca-Alginate?
Binds to the free oxygen group, linking polymer chains together
How does Glytaraldehyde chemically cross link Chitosan? And what functional group is formed?
- Binds to the Nitrogen
- Forming a schiff base functional group (C=N)
If we want to reduce the release rate of a drug from a hydrogel matrix, how can we do this, by specifically increasing the interactions the drug has with the hydrogel? (2)
1) Physical method, charge the hydrogel oppositely to the drug, so they are bound together more
2) Chemical method, Add a cleavable crosslinker that links the active drug to the hydrogel polymer chain (need to make sure its cleavable when needed)
What 2 methods are there for reducing the rate of drug release from hydrogels by specifically increasing the diffusion barrier?
1) Composite hydrogels: increase the number of barriers by encapsulate the drug in a miicrogel/microparticle within a hydrogel
2) Surface modification: surface modifying the hydrogel so that its coated in proteins that reduce drug flux
Give an example of a surface modifying polymer that reduces the release rate of a drug from the hydrogel matrix and explain how it operates
- PNIPAM
- PNIPAM is a temperature sensitive polymer that can be grafted onto a hydrogel surface
- At high temperatures it collapses into a thick globular shape, coating the surface reducing drug release
- At low temps, it undergoes a physical change to a coil shape, opening space to allow the drugs to diffuse out
Describe 3 methods that have been developed to enable the incorporation of non-water soluble drugs into hydrogels?
1) Adding hydrophobic monomers into the hydrogel polymer chain, causes hydrophobic drugs to aggregate with the monomers
2) Grafting hydrophobic side chains onto the hydrogel polymer chains, facilitates hydrophobic drug interactions
3) Cyclodextrin is water soluble compound but has a hydrophobic cavity that can encompass and carry hydrophobic molecules
- All these methods essentially create a microenvironment for the environment facilitating increased solubility
do you know these
