Biological hydrogels as selective diffusion barriers
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Biological hydrogels as selective diffusion barriers
- 1. Biological hydrogels as selective diffusion barriers Ortal Levi Department Of Chemical Engineering June 2013
- 2. 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
- 3. 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
- 4. 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 MechanicalMechanical strength andstrength and permeabilitypermeability Cross-linking and/or copolymerization with hydrophobic comonomers density↑, mechanical strength↑, swelling property↓
- 5. (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.
- 6. Hydrogel FabricationHydrogel Fabrication Chemical 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
- 7. Hydrogel FabricationHydrogel Fabrication Physical crosslinking • Ionic hydrogel Chemical and Physical crosslinking • Cross-linking without chemical reaction • ionic interaction, hydrogen bonding, antigen-antibody interaction, supramolecular association
- 8. Hydrogel FabricationHydrogel Fabrication + MonomerCrosslinker Vinyl group-containing water-soluble polymers Copolymerizatio n Polymerization Hydrogel network Chemical crosslinking Polymerization of water soluble monomers in the presence of bi- or multifunctional cross-linking agent or
- 9. Applications of Hydrogels in Drug DeliveryApplications of Hydrogels in Drug Delivery - 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
- 10. Applications of Hydrogels in Drug DeliveryApplications of Hydrogels in Drug Delivery 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 gel Change in pH for gel swelling Drug release through the swollen network Drug release by the squeezing action Change in temperature for gel collapse
- 11. DiffusionDiffusion Random Walk Fick’s Law Model discrimination for the propionic acid diffusion into hydrogel beads using lifetime confocal laser scanning microscopy
- 12. time Water-insoluble Polymer 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
- 13. filtering mechanisms in biological hydrogels Mesh Size Electrostatic, ionic strength Diffusion of Particles in the Extracellular Matrix: The Effect of Repulsive Electrostatic Interactions
- 14. Filtering-Electrostatic interactionFiltering-Electrostatic interaction Diffusion of Particles in the Extracellular Matrix: The Effect of Repulsive Electrostatic Interactions Cross Section Collagen Fibers in C.V
- 15. Filtering-Electrostatic interactionFiltering-Electrostatic interaction Low fiber mol. fraction High fiber mol. fraction Diffusion of Particles in the Extracellular Matrix: The Effect of Repulsive Electrostatic Interactions
- 16. Filtering-Electrostatic interactionFiltering-Electrostatic interaction • Ionic strength masking Decreasing diffusion coefficient with increase in ionic strength Diffusion of Particles in the Extracellular Matrix: The Effect of Repulsive Electrostatic Interactions
- 17. Filtering-Size ExclusionFiltering-Size Exclusion • The hydrogel scaffold-TEM Different structures Synthesis and characterization of disulfide-crosslinked alginate hydrogel scaffolds
- 18. 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
Notas do Editor
- Swelling ratio 는 하이드로겔이 물을 흡수하는 정도를 나타나는데 이것은 swelling 하이드로겔 무게 값을 dried 된 하이드로겔 무게 값을 뺸 값응 다시 dried 하이드로겔 값으로 나눈 값입니다 . Swelling ratio 는 모노머의 유형과 조성 , 주변환경 요소 , 가교 밀고에 따라 달라 질수 있습니다 . 가교밀도는 하이드로겔의 기계적 강도와 하이드로겔에 물이 침투하는 성질에 많은 영향을 주게 됩니다 . 가교 밀도가 높고 , 하이드로겔이 IPN 구조이면서 소수성 모노머들이 공중합 되어 있으면 기계적 강도는 높아지지만 swelling 은 낮아지게 됩니다 . 이러한 성질을 이용하여 우리가 원하고자 하는 물성을 갖는 하이드로겔을 만들수가 있습니다 .
- 하이드로겔은 화학적 , 물리적 결합으로 이루어진 하이드로겔로 나누어집니다 . 화학적 결합 하이드로겔은 공유결합으로 가교 되어 있으며 열경화서 하이드로겔입니다 . 그리고 부피 상 전이가 일어나며 모양이 안정하고 잘 변하지 않습니다 . 반면에 물리적 결합으로 이루어진 하이드로겔은 수소결합 , 소수성 상호작용 등과 같은 비공유 결합으로 이루어져 있으며 열가소성 하이드로겔입니다 . 이것은 sol-gel transition 이 일어나며 모양 안정성과 그 모양을 유지하는 데 제한적인 특징이 있습니다 .
- 화학적 가교는 두개 이상의 작용기를 가지고 있는 가교제 존재하에서 물에 잘 녹는 모노머들의 중합으로 생성합니다 . 그림에서 보시다시피 모노머가 가교제와 공중합이 일어나면서 하이드로겔 망상조직을 형성하는 것과 vinyl 그룹을 가진 물에 잘녹는 고분자를 중합하여 하이드로겔 망상조직을 생성할 수 있습니다 . 이것은 앞에서 말했다시피 공유결합으로 이루어진 화학적 결합으로 이루어진 하이드로겔입니다 .