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