acidic and basic groups on polmyer make them useful to crosslink to form hydrogel

1. HYDROGEL POLYMER IN
DRUG DELIVERY
Amber Bano
International Center of Chemical and Biological Sciences
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Supervisor: Dr. Imran Malik

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3. Outline
• Hydrogel for controlling drug dosage
• Hydrogel
• Problem statement
• Hydrogel classification
• Hydrogel Properties
• How to extend effectiveness of hydrogel for drug delivery
• Challenges to improve applicability of hydrogels
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4. Hydrogel for controlling drug dosage
• The purpose of coating polymer in drug loaded
nanoparticles to target the pathological cells in order to
increase effectiveness of drug
• Allow the smaller molecular weight drugs to access
their interior
• Swell at target site to release drug
• Protects drug from physiological environment
• Reduce drug side-effects 4

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6. Water Soluble Polymers and the Hydrogel
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7. Problem Statement
How to increase effectiveness of
hydrogel for targeted drug delivery
???
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8. Hydrogel
• Hydrogel is formed via the cross-linking of water-
soluble polymers
• Cross-links are of two general categories: physical and
chemical.
• Hydrogel structures may contain hydrophilic units in
the polymer backbone and side chain
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9. • It contains: -OH, -COOH,-SO3H, -CONH2
• Polymers with hydrophilic units in the backbone
:polyvinyl alcohol, N-vinly-2-pyrrolidione, acryl amid
containing materials poly(N-isopropylacrylamide),
PNIPAM, derivatives of polyethylene oxide, and
ionomers and glycopolymers
• It can be formulated in a variety of physical forms:
Slabs, spheres, coatings, and films
Hydrogel
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10. Hydrogel Classification
Based on synthesis route
Based on configuration
Based on cross-linking
Based on ionic charges present on polymer networks
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11. Based on synthesis route
• Homopolymer hydrogel
• Copolymer hydrogel
• Multiple hydrogels or Interpenetrating polymeric
hydrogel (IPN)
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12. Based on configuration
• Amorphous hydrogels
• Semi crystalline hydrogels
• Crystalline
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13. Based on cross-linking
Physical crosslinking:
• Physical networks have transient junctions that arise from either
polymer chain entanglements or physical interactions such as
ionic interactions(calcium alginate), hydrogen bonds, or
hydrophobic interactions. It is reversible.
• No cross linker is needed
Chemical cross linking:
• Consist of chemically irreversible covalent cross-linked bonds
• It is a direct reaction of linear and branched polymer chains with
a small molecular weight bi-functional chemical such as
glutaraldehyde.
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14. Based on ionic charges present on polymer
networks
Cationic
Anionic
Neutral
Amphoteric
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Based on ionic charges present on polymer
networks
Collagen Gelatin
Agarose

16. Hydrogel Properties
Why hydrogels are used in drug delivery systems?
• Biocompatible
• Biodegradable
• Swelling property
• Environment sensitivity
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17. Biocompatible
• It contains high water content
• Hence less toxic
• Behaves like body tissue
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18. Biodegradable
• Physical: erosion of polymer
• Chemical: dissolution(ionization) and diffusion
(mixing solubilization with medium particles) process
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19. Swelling property
• Depend on type and composition of monomer
• Depend on cross-linking
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20. Environment sensitivity
Hydrogel behavior to adapt
structural changes in response to
various physical and chemical
triggers
Example: Physical: Temperature,
electric or magnetic field, light,
pressure, and sound. Chemical:
stimuli include pH, solvent
composition, ionic strength, and
molecular species 20

21. EXAMPLE: Sodium alginate
• It is the water-soluble linear polysaccharide
• Decreasing pH(acidic) causes the precipitation of the alginate
biopolymer
• Ionic strength and gelling ions affect the solubility of the alginate salts
• Alginates are extracted from three species of brown-algae-cell walls
• Sodium form hydrogel because of the substitution of Na+ of the
guluronic acid residues by different divalent cations (Ca2+, Sr2+, Ba2+,
and etc.). The divalent cation binds to the α-L-guluronic block (and
between two different chains), a 3D network is formed
• Chemical structures of Alginate depended on the source of the Alginate
polymer
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22. Methods to produce Alginate hydrogel
• Ionic crosslinking
• Covalent cross linking
The crosslinking of the natural and synthetic polymers could be
achieved through the chemical reaction of hydrogel functional
groups (including -OH, −COOH, and -NH2) with crosslinkers
such as glutaraldehyde, adipic acid di hydrazide, poly (ethylene
glycol)-diamine by aldol condensation and Michael addition
• Phase transition
PNIPAM(LCST 32 °C) into the backbone of alginate
• Free radical polymerization 22

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24. • Alginate hydrogels can absorb high-water content, nontoxic, soft
consistency, biocompatible, biodegradable drug carriers to deliver the
low molecular weight drugs and macromolecules including proteins
and genes
• The drug could encapsulate in pores of the carriers.
• Depending on the pH of the surrounding medium, ALG could form
two types of gels. At low pH (gastric environment) it shrinks and
produces a viscose acidic gel which does not release its encapsulated
drugs.
• Passing intestinal tract with higher pH, the skin-like structure of
alginic acid converted to the soluble viscose gel, in which the
disruption of the polymeric network causes drug dissolution and
release.
• The drug releases from the pores of the hydrogel are carried out by
the various mechanisms including diffusion-controlled, swelling
controlled, chemically controlled and environmentally-responsive
release
Alginate-based drug delivery vehicles for
cancer treatment
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25. Alginate-based vehicles
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26. EXAMPLE: Chistosan
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27. EXAMPLE: Gelatin and Chitosan hydrogels
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Cross-linker
sodium sulfate and
magnesium sulfate

28. Challenges to improve applicability of hydrogels
• Improve delivery of hydrophobic drug
• Improve the kinetics of drug release profile
• Inefficient for large molecules such as nucleic acid,
antibodies, proteins etc.
• Improving the clinical usage
• Increase anti-toxicity of hydrogels
• Making them more biocompatible
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29. References
• https://books.google.mw/books?id=TBLOBQAAQBAJ&printsec=copyright
• https://books.google.com/books/about/Introduction_to_Polymer_Chemistry_Th
ird.html?id=nmHzgroEYIwC
• https://pubs.acs.org/doi/pdf/10.1021/ba-1996-0248.ch001
• Abasalizadeh, F., Moghaddam, S. V., Alizadeh, E., Kashani, E., Fazljou, S. M. B.,
Torbati, M., & Akbarzadeh, A. (2020). Alginate-based hydrogels as drug delivery
vehicles in cancer treatment and their applications in wound dressing and 3D
bioprinting. Journal of biological engineering, 14(1), 1-22.
• Ahmed, E. M. (2015). Hydrogel: Preparation, characterization, and applications: A
review. Journal of advanced research, 6(2), 105-121.
• https://pubs.acs.org/doi/10.1021/bm200731x
• https://www.researchgate.net/publication/236840222_Ionically_and_Covalentl
y_Cross-Linked_Hydrogels_Based_on_Gelatin_and_Chitosan 29

30. References
• https://www.sciencedirect.com/science/article/pii/S
2090123213000969#b0080
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31. THANK YOU
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