Biological hydrogels as selective diffusion barriers
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Transcript of Biological hydrogels as selective diffusion barriers
Biological hydrogels as selective diffusion barriers
Ortal LeviDepartment Of Chemical EngineeringJune 2013
DefinitionDefinition• Three-dimensional networks of hydrophilic
polymer chains that do not dissolve but can swell in water
• both solid like and liquid like properties• high biocompatibility• environmental stimuli respondent
(temperature, pH, light, specific molecules)
• Ideal for controlled drug delivery
ClassificationClassification -various criteria for the classification of hydrogels
Origin Natural
Synthetic
Water content or degree of swelling
Low swelling
Medium swelling
High swelling
Superabsorbent
Porosity Nonporous
Microporous
Macroporous
Superporous
Cross-linking Chemical (covalent bonding)
Physical (noncovalent bonding)
Biodegradability Biodegradable
Nondegradable
Properties and Structures of HydrogelsProperties and Structures of Hydrogels
Rs = (Ws-Wd) / Wd
Rs = swelling ratio
Ws = weight of swollen hydrogels
Wd = weight of dried hydrogels
Swelling property is influenced by:•type and composition of monomers•other environmental factors such as :
temperature, pH, ionic strength•cross-linking Mechanical Mechanical
strength and strength and permeabilitypermeability
Cross-linking and/or copolymerization with hydrophobic comonomers density↑, mechanical strength↑, swelling property↓
(a )Degradation of the hydrogel at different temperatures in PBS. )b( Swelling kinetics of the hydrogel at different temperatures. )c( Entrapped GFs in hydrogel in PBS. )d( Cumulative release profiles of GFs from hydrogel.
Hydrogel FabricationHydrogel FabricationChemical hydrogels
Physical hydrogels
▪ Hydrogen bonding
▪ hydrophobic interaction
▪ crystallinity
▪ stereocomplex formation
▪ ionic complexation
Covalently crosslinked
Noncovalently crosslinked
Thermoset hydrogels
Thermoplastic hydrogels
Volume phase transition
Sol-gel phase transition
Reliable shape stability and memory
Limited shape stability and memory
Hydrogel FabricationHydrogel FabricationPhysical crosslinking
• Ionic hydrogel
Chemical and Physical crosslinking
• Cross-linking without chemical reaction
• ionic interaction, hydrogen bonding, antigen-antibody interaction, supramolecular association
Hydrogel FabricationHydrogel Fabrication
+
Monomer
Crosslinker
Vinyl group-containing water-soluble polymers
Copolymerization
Polymerization
Hydrogel network
Chemical crosslinking
Polymerization of water soluble monomers in the presence of bi- or multifunctional cross-linking agent
or
Applications of Hydrogels in Drug Applications of Hydrogels in Drug
DeliveryDelivery
- Benefits of controlled drug delivery more effective therapies with reduced side effects the maintenance of effective drug concentration
levels in the blood patient’s convenience as medicines hence increased
patient compliance
- Release mechanisms of drug molecules
: diffusion, dissolution, osmosis, ion exchange
Applications of Hydrogels in Drug Applications of Hydrogels in Drug
DeliveryDelivery Environment-Sensitive Hydrogels
• respond to environmental change : temperature, pH, specific molecule• reversible volume phase transition or sol-gel phase transition• “intelligent” or “smart” hydrogel
Drug-loaded gelChange in pH for gel swelling
Drug release through the swollen network
Drug release by the squeezing action
Change in temperature for gel collapse
DiffusionDiffusion
Random Walk
Fick’s Law
Model discrimination for the propionic acid diffusion into hydrogel beads using lifetime confocal laser scanning microscopy
time
Water-insolublePolymer membrane
Applications of Hydrogels in Drug DeliveryApplications of Hydrogels in Drug Delivery
Reservoir system
Biological self-assembly of injectable hydrogel as cell scaffold via specific nucleobase pairing
filtering mechanisms in biological hydrogels
Mesh Size Electrostatic, ionic strength
Diffusion of Particles in the Extracellular Matrix: The Effect of Repulsive Electrostatic Interactions
Filtering-Electrostatic Filtering-Electrostatic
interactioninteraction
Diffusion of Particles in the Extracellular Matrix: The Effect of Repulsive Electrostatic Interactions
Cross Section
Collagen Fibers in C.V
Filtering-Electrostatic Filtering-Electrostatic
interactioninteraction
Low fiber mol. fraction
High fiber mol. fraction
Diffusion of Particles in the Extracellular Matrix: The Effect of Repulsive Electrostatic Interactions
Filtering-Electrostatic Filtering-Electrostatic
interactioninteraction
• Ionic strength masking
Decreasing diffusion coefficient with increase in ionic strength
Diffusion of Particles in the Extracellular Matrix: The Effect of Repulsive Electrostatic Interactions
Filtering-Size ExclusionFiltering-Size Exclusion
• The hydrogel scaffold-TEMDifferent structures
Synthesis and characterization of disulfide-crosslinked alginate hydrogel scaffolds
SummarySummary
• Hydrogels have played role in the development of various controlled-release formulation
• biocompatible and increasing the solubility of poorly soluble drug
• Hydrogels with novel properties will continue to play important role in drug delivery
• smart hydrogels and new controlled-release formulation